November 12, 2014

You might think that the “kiss-and-hop” is a dance move strictly forbidden at a Duggar homeschool prom, but it refers to the quick dynamics of the microtubule-associated protein tau. Today’s image is from a paper describing unexpected results about how tau resides on and regulate microtubules without physically impeding microtubule motors. 

The microtubule-associate protein tau binds to and stabilizes the microtubules within an axon. As most tau is believed to decorate axonal microtubules, it was previously unclear how tau can function in its non-microtubule-dependent roles, or how the presence of tau does not interfere with microtubule motors and axonal transport. A recent paper by Janning and colleagues describes the use of single-molecule tracking of tau in living cells. Janning and colleagues found that tau resides on a single microtubule for 40ms before hopping to the next microtubule, and that this unexpectedly short residence time is sufficient to affect microtubule stability. This “kiss-and-hop” mechanism allows for normal axonal transport, and suggests how some tau functions away from microtubules. In the images above, tau (red) is labeled in mouse cortical neurons, as are microtubules (green) and the nucleus (blue).  

Janning, D., Igaev, M., Sundermann, F., Bruhmann, J., Beutel, O., Heinisch, J., Bakota, L., Piehler, J., Junge, W., & Brandt, R. (2014). Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons Molecular Biology of the Cell, 25 (22), 3541-3551 DOI: 10.1091/mbc.E14-06-1099

October 24, 2014

There is a party going on at the ends of microtubules, but I wasn’t invited. That won’t stop me, or countless cell biologists out there, from peeping in the window to check out all of the microtubule shenanigans. Today’s image is from a paper describing how Doublecortin binds to microtubule ends.

The plus end of a microtubule is the primary site for growth and shrinkage, and interaction with several microtubule-associate proteins. Different microtubule end-binding proteins may interact with microtubules using different mechanisms: the end-binding protein EB1 relies on the nucleotide state of the tubulin at the microtubule end, while a recent paper shows how another protein, Doublecortin (DCX), relies on the curvature of microtubule ends for binding. DCX is a neuronal microtubule-associate protein that plays an important role throughout development, yet how it interacted with microtubule ends was previously unclear. Bechstedt and colleagues used single-molecule microscopy to show that DCX (images above, green in merged) binds with higher affinity to curved microtubules (magenta) than to straight microtubules. DCX mutations, which are found in patients with double cortex syndrome, prevent the protein from binding to curved regions of microtubules.

Bechstedt, S., Lu, K., & Brouhard, G. (2014). Doublecortin Recognizes the Longitudinal Curvature of the Microtubule End and Lattice Current Biology, 24 (20), 2366-2375 DOI: 10.1016/j.cub.2014.08.039
Copyright ©2014 Elsevier Ltd. All rights reserved.

September 17, 2014

All good things must end—even the focal adhesions that are so key to cell migration. Today’s notable image is the first live cell visualization of ECM degradation at focal adhesions, in a recent paper that reports the link between CLASPs, exocytosis, and focal adhesion turnover. 

Cell migration depends on the precisely-timed formation of focal adhesions (FAs) that link the crawling cell to the extracellular matrix (ECM). FAs serve as anchor points for the crawling cell, yet must later disassemble in order to allow continued movement of the cell. A recent paper describes how CLASP proteins link FA-associated microtubules, exocytosis, and FA turnover. CLASP proteins are +TIP proteins, which means that they are found on the growing ends of microtubules. Stehbens and colleagues found that the clustering of CLASPs around FAs correlates with the timing of FA disassembly, and that CLASPs are required for ECM degradation. Stehbens and colleagues also found that the tethering of microtubules to FAs, via CLASPs, serve as a transport pathway for exocytic vesicles at FAs. The images above are the first live cell images of ECM degradation (visualized as dark regions, top panel) at FAs (magenta).

BONUS! For more information on the scanning angle interference microscopy used in this paper, check out Matthew Paszek’s Nature Methods paper here.

Stehbens, S., Paszek, M., Pemble, H., Ettinger, A., Gierke, S., & Wittmann, T. (2014). CLASPs link focal-adhesion-associated microtubule capture to localized exocytosis and adhesion site turnover Nature Cell Biology, 16 (6), 561-573 DOI: 10.1038/ncb2975
Adapted by permission from Macmillan Publishers Ltd, copyright ©2014

August 21, 2014

Microtubules are known for their fascinating dynamics, but some cellular processes require a more stable microtubule cytoskeleton. Thankfully, these stable, acetylated microtubules are just as photogenic as their non-modified microtubule pals. Today’s image is from a paper describing the role of the protein paxillin in microtubule acetylation. 

Crawling cells require coordination of adhesive forces, cytoskeletal rearrangements, and cell polarization. Cell polarization helps to direct newly synthesized proteins to the leading edge of the crawling cell, relying on both a stable microtubule cytoskeleton and positioning of the Golgi apparatus in front of the nucleus. The stability of these long-lived microtubules is due to acetylation—a post-translational modification of α-tubulin. A recent study by Deakin and Turner uncovered a role for the focal adhesion scaffolding protein paxillin in regulating microtubule acetylation, which in turn regulates Golgi integrity and cell polarization. Paxillin modulates microtubule stability through its inhibition of HDAC6, an α-tubulin deacetylase, and does so in both normal and transformed cells. In the images above, depletion of paxillin (bottom) in malignant (left column) and normal (right column) cell types resulted in a drop of microtubule acetylation (yellow), compared to control cells (top).

Deakin, N., & Turner, C. (2014). Paxillin inhibits HDAC6 to regulate microtubule acetylation, Golgi structure, and polarized migration originally published in the Journal of Cell Biology, 206 (3), 395-413 DOI: 10.1083/jcb.201403039

June 10, 2014

The Life History of a Single Kinetochore Fiber sounds like a book a lot of us would enjoy (well, me at least). It isn’t really a book about a plucky kinetochore fiber who triumphs over a difficult childhood, but rather the focus of a fascinating recent paper. In this paper published in Molecular Biology of the Cell, LaFountain and Oldenbourg present results showing a model for kinetochore microtubule formation that occurs at kinetochores.

Kinetochore fibers link chromosomes to the mitotic spindle, which drives chromosome segregation during anaphase. The prevailing model of kinetochore fiber formation includes a “search and capture” mechanism, in which some dynamic spindle microtubules reach a kinetochore and become stabilized by the interaction. A recent paper by LaFountain and Oldenbourg shows, however, that the maturation of these kinetochore fibers depends on the addition of microtubules at the kinetochore-proximal end, with polymerization towards the spindle pole. In this study, the naturally birefringent microtubules of crane-fly spermatocytes were examined, allowing a quantitative analysis of where microtubules are added. In the images above, kinetochore-proximal addition of microtubules can be seen in the centrosome-free half-spindle (red arrows) of a crane-fly spermatocyte, from early prometaphase to metaphase (top to bottom).

LaFountain, J., & Oldenbourg, R. (2014). Kinetochore-driven outgrowth of microtubules is a central contributor to kinetochore fiber maturation in crane-fly spermatocytes Molecular Biology of the Cell, 25 (9), 1437-1445 DOI: 10.1091/mbc.E14-01-0008

April 30, 2014

Have you ever driven in the wrong direction on a one-way street. It feels as wrong as a hamburger smoothie and you feel overwhelmed with panic. It’s important to go the right direction on one-way streets, and a neuron understands this. Neurons are polarized so that signals can come and go in the right direction. Today’s stunning image is from a paper describing the cytoskeletal architecture within a region of a neuron that’s important for polarity. 

The axon initial segment (AIS) is the part of an axon closest to the neuron’s cell body, and is the site of action potential initiation. The AIS is crucial for the neuron’s polarity, which facilitates the direction of incoming signals (coming in from dendrites) and outgoing information (out along the axon to the synapse). A recent study from Jones and colleagues investigated how the AIS maintains neuronal polarity. Jones and colleagues used platinum replica electron microscopy (PREM) to image the cytoskeleton in hippocampal neurons, and found that it begins with a bundle of microtubules. A dense fibrillar–globular coat covers this microtubule bundle and contains many proteins as well as actin filaments. Actin filaments are found in two sparse populations—either stable, short filaments or dynamic, long filaments. Jones and colleagues propose that the dynamic actin filaments play a role in the AIS coat, while the stable filaments may play a structural role in the AIS diffusion barrier. This diffusion barrier prevents the mixing of plasma membrane components from dendrites and axons, an important factor in maintaining polarity. The image above shows microtubules within the AIS, with thin fibrils (arrows) and a fibrillar coat over the microtubules (arrowheads) visible.

Jones, S., Korobova, F., & Svitkina, T. (2014). Axon initial segment cytoskeleton comprises a multiprotein submembranous coat containing sparse actin filaments originally published in the Journal of Cell Biology, 205 (1), 67-81 DOI: 10.1083/jcb.201401045

January 15, 2014

The mitotic spindle seems to get all the fun of a microtubule-dynein party, but do not fret. A recent paper describes some cool interactions of microtubules with dynein at the cell’s cortex.

The molecular motor dynein walks along microtubules, and this movement can do great things by moving the microtubules themselves or moving material along the microtubule. Recent work found that dynein at the cell’s cortex may influence cell motility using an actin-independent mechanism that pushes microtubules along the cortex. In an even more recent paper in the journal Molecular Biology of the Cell, this same research group shows these cortical dynein-microtubule interactions directly. Using TIRF microscopy, Mazel and colleagues found speckles of cortical dynein complexes associated with microtubules. These microtubules can move, bend, and even rotate around these speckles. The images above show the difference between wide-field microscopy (left) and TIRFM (right) when imaging microtubules at the cortex. In the bottom panel, a short microtubule can be seen moving directionally.


Tomáš Mazel, Anja Biesemann, Magda Krejczy, Janos Nowald, Olga Müller, & Leif Dehmelt (2014). Direct observation of microtubule pushing by cortical dynein in living cells Molecular Biology of the Cell, 25 (1) DOI: 10.1091/mbc.E13-07-0376

June 4, 2013

HighMag is back from an early summer vacation at the beach, and ready to get our microscopic groove on.  Happy Summer, everyone!

Our world is the same size it’s always been, but so many advances in technology have made the world seem a lot smaller.  We can call our brother across the country and video chat with our sister on the other side of the world, all while searching the internet for the lyrics to Snow’s “Informer” (side note…knowing the lyrics won’t help you understand the song AT ALL).  Similarly, a neuron’s axons make the nervous system seem a lot smaller too, with their amazing ability to grow very long.  Today’s image is from a paper showing how microtubule sliding is involved.

Neurons can transmit signals to far away neurons, thanks to the ability of their axons to grow insanely long.  Both actin filaments and microtubules participate in axon growth, with microtubules pushing the growing axon out and actin filaments working directly at the tip of the growing axon, called the growth cone.  A recent paper shows the role of microtubule sliding in the initial growth of neurites in fruit fly neurons.  Lu and colleagues found that the microtubule motor kinesin-1 drives the sliding of microtubules past one other in order to push out the neuron’s growing projection.  This mechanism does not require actin filaments, and is suppressed during maturation of neurons.  In the images above, microtubules (green) can be seen pushing against the tip of a growing neurite in a young neuron (membrane of neuron in red and bottom right series).  The whole neuron is on the left, and the neurite in the boxed region is shown in the time-lapse images on the right.

Lu, W., Fox, P., Lakonishok, M., Davidson, M., & Gelfand, V. (2013). Initial Neurite Outgrowth in Drosophila Neurons Is Driven by Kinesin-Powered Microtubule Sliding Current Biology, 23 (11), 1018-1023 DOI: 10.1016/j.cub.2013.04.050 
Copyright ©2013 Elsevier Ltd. All rights reserved.

May 2, 2013

If cells had their own soundtracks, I think any flagella-wielding cells would take home the prize.  Maybe the soundtrack begins on a high note with Devo’s “Whip It!”, continues on to the more crass Clarence Carter, plateaus with some headbanging death metal, and finally pays homage to Flock of Seagulls simply due to their flagellar waveform hair.  Today’s image is from a paper describing an outer-inner dynein link in flagella.

Flagella are whip-like organelles protruding from cells, and function to move fluid past the cell to generate motility.  In flagella, nine doublets of microtubules are bundled around a central microtubule pair (the 9+2 structure).  Outer dynein arms (ODAs) and inner dynein arms (IDAs) drive movement of the microtubule doublets past each other, generating the flagellar beating motion.  The ODA and IDA play distinct roles in flagellar function, but a recent paper finds a link between them.  Oda and colleagues found that intermediate chain 2 (IC2) of ODAs functions as part of the outer-inner dynein linker.  IC2 is a hub between ODAs and IDAs to regulate flagellar beating, based on the beating motion of IC2 mutants in the green algae Chlamydomonas.  The images above show the waveforms and image sequences of swimming Chlamydomonas cells.  The bending of flagella in wild-type cells (top row) is different from that of ic2 mutant cells (bottom row).  The principle bend at the flagellar tip in the forward stroke persists in the mutant (arrowhead); this altered bending results in slower swimming for the mutants.

Oda, T., Yagi, T., Yanagisawa, H., & Kikkawa, M. (2013). Identification of the Outer-Inner Dynein Linker as a Hub Controller for Axonemal Dynein Activities Current Biology, 23 (8), 656-664 DOI: 10.1016/j.cub.2013.03.028
Copyright ©2013 Elsevier Ltd. All rights reserved.

March 22, 2013

If there was an NCAA-type bracket of cool things to image in a cell, I’m pretty sure a spindle would make it pretty far in the tournament—if not take the whole thing.  They are extremely photogenic, and their important role and dynamic nature make them a top seed for sure.  Today’s image is from a paper identifying a new player in spindle positioning.

The position of the mitotic spindle serves as the guide to where the cell will be divided into two daughter cells in cytokinesis.  The spindle is positioned with the help of astral microtubules—microtubules that grow from the centrosomes toward the cell periphery.  The interaction of these microtubules with machinery at the cell’s cortex can generate pulling or pushing forces that position the entire mitotic spindle, yet this interaction isn’t completely understood.  A recent paper identifies a protein called MISP as a player in the microtubule-cortex interaction.  Zhu and colleagues found that depletion of MISP, an actin-binding protein, resulted in shortened astral microtubules and rocking, misoriented spindles, among other mitotic defects.  Zhu and colleagues showed that MISP is phosphorylated by Plk1, a major kinase important in many mitotic processes.  The images above show MISP (gray, red in merged images) localization throughout mitosis.  MISP is localized to cortical actin (green).  Boxed regions are shown in higher magnification in the insets.  

Zhu M, Settele F, Kotak S, Sanchez-Pulido L, Ehret L, Ponting CP, Gönczy P, & Hoffmann I (2013). MISP is a novel Plk1 substrate required for proper spindle orientation and mitotic progression. originally published in the Journal of Cell Biology, 200 (6), 773-87 PMID: 23509069

February 19, 2013

No matter how long you’ve been with your partner, sometimes he or she reveals a hidden talent that you’re just amazed to witness for the first time.  Maybe it’s his or her plate-spinning routine, amazing juggling, or a surprise skill at carving flowers out of radishes.  One day I will surprise my husband with my own hidden talent, once I find it, and he will wonder if it’s normal for one person to love another so much.  Today’s image is from a paper showing microtubules branching from existing microtubules…branching!  Is it normal for one person to love microtubules so much?!

Microtubules are dynamic filaments required in countless cellular processes, so their nucleation and growth has always been a point of interest for many biologists.  Microtubule nucleation from centrosomes is the best understood mechanism for microtubule nucleation, yet centrosomes are not always necessary for microtubule growth within a mitotic spindle.  A recent paper shows direct evidence for microtubule nucleation from existing microtubules in meiotic frog extracts, through the use of TIRF microscopy.  Petry and colleagues show that these new daughter microtubules nucleate from existing microtubules at a low “branch” angle.  In addition, daughter microtubules have the same polarity as mother microtubules, which can help maintain mitotic spindle integrity.   Branching microtubule nucleation requires γ-tubuin and augmin, a protein that increases microtubule density.  RanGTP, which is required for chromatin-mediated microtubule nucleation, and its effector protein TPX2 both stimulate branching microtubule nucleation.  In the images above, microtubules branch from existing microtubules after the addition of both RanGTP and TPX2, resulting in fan-like microtubule structures.  Lower panel is an enlarged view of the area marked with the asterisk.  Long arrows point to daughter microtubules nucleating at a clear branched angle, while short arrows point to daughter microtubules growing along the length of mother microtubules.

BONUS!!  Here's a mesmerizing movie of branching microtubules after the addition of RanGTP and TPX2, similar to the above image.

Petry, S., Groen, A., Ishihara, K., Mitchison, T., & Vale, R. (2013). Branching Microtubule Nucleation in Xenopus Egg Extracts Mediated by Augmin and TPX2 Cell, 152 (4), 768-777 DOI: 10.1016/j.cell.2012.12.044 
Copyright ©2013 Elsevier Ltd. All rights reserved.

February 7, 2013

The alphabet soup of cell biology can be overwhelming, but APC is one jumble of letters that most cell biologists are very familiar with.  APC is a protein that functions in cell division and development, and is the most commonly mutated gene in colon cancer.  Today’s image is from a paper describing another hat that APC gets to wear—a role in the interaction between microtubules and intermediate filaments.

Intermediate filaments (IFs) and microtubules are both part of the cell’s cytoskeleton, and their interactions together during different cellular processes have brought attention to the possible proteins that guide these interactions.  IFs function in cell migration, and a recent paper describes rearrangements of the IF network during the migration of astrocytes, cells that provide nutritional and structural support for neurons in the brain.  Sakamoto and colleagues found that the tumor suppressor protein APC (adenomatous polyposis coli) is required for microtubule-IF interactions and for the microtubule-based rearrangements of the IF network in migrating astrocytes.  Loss of APC resulted in a disorganized IF network in glioma and carcinoma cells.  The images above show microtubule-APC-IF interactions in a migrating astrocyte, with fluorescently labeled IFs (vimentin, green), APC (red), and microtubules (blue).  Arrowheads point to APC along microtubules, while arrows point to both IFs and APC along microtubules.

Sakamoto, Y., Boeda, B., & Etienne-Manneville, S. (2013). APC binds intermediate filaments and is required for their reorganization during cell migration originally published in the Journal of Cell Biology, 200 (3), 249-258 DOI: 10.1083/jcb.201206010

January 28, 2013

In my many hours in a dark microscopy suite, I would stare slack-jawed at cells going through mitosis like a perv at a peep show. Beneath the grace of this serious cellular rite of passage is a massive amount of regulation, which just adds to the fascination so many biologists have for the event. Today’s image is from a paper that describes the generation and importance of forces that help align chromosomes on a metaphase plate.

During mitosis, chromosomes must align on the metaphase plate with attachments to opposite spindle poles. Only after this precise alignment can the cell begin a cascade of signals and checkpoints to trigger anaphase, which segregates sister chromatids into their eventual daughter cells. Chromosome alignment gets a hand from polar ejection forces (PEFs), which are forces generated by the microtubule-based motor kinesin found on chromosome arms. These chromokinsesins (kinesin-10 family members) are thought to walk chromosome arms away from spindle poles along microtubules, and are important for timely congression of chromosomes to the metaphase plate. A recent paper describes the relationship between PEFs and the stability of spindle-chromosome attachments. Cane and colleagues manipulated the levels of the fruit fly kinesin-10 protein NOD to similarly manipulate the tension and forces applied to chromosomes. When both kinetochores of a chromosome pair were incorrectly attached to the same spindle pole (called a syntelic attachment), NOD stabilized the attachments by preventing error correction by the protein Aurora B. From their results, Cane and colleagues show that PEFs regulate the stability of kinetochore attachment to spindle microtubules. In the time-lapse images above, NOD overexpression in a fruit fly cell caused an abnormal metaphase plate to form. Despite the syntelic attachments of many chromosomes, the cell still entered anaphase (AO), resulting in daughter cells with too many nuclei (far right image). NOD signal is red, microtubules are green. 

BONUS!!  Beautiful movies from the paper can be found here.

Cane, S., Ye, A., Luks-Morgan, S., & Maresca, T. (2013). Elevated polar ejection forces stabilize kinetochore-microtubule attachments originally published in the Journal of Cell Biology, 200 (2), 203-218 DOI: 10.1083/jcb.201211119

December 10, 2012

A cell is nothing if not thorough. A cell can regulate a function with one method, but usually employs several methods of regulation to get a job done, ensure that it gets done correctly, and has a backup plan if it goes awry. Today’s image is from a paper describing regulation of a protein by localized levels of mRNA.

For some types of cells, notably polarized cells, the localization of a protein can be regulated through mRNAs. mRNAs are transcribed from DNA, and then later translated into the proteins that function throughout the cell. By transporting mRNAs to specific regions, the cell in turn can have localized levels of proteins. A recent paper shows the specific localization of an mRNA encoding the signaling molecule MKK7 to neuronal growth cones, which are dynamic extension of a developing axon searching for its final target. According to Feltrin and colleagues, this localization of MKK7 mRNA may result in localized levels of MKK7 protein. MKK7 mRNA localization modulates JNK signaling, which in turn regulates microtubule bundling during neuronal outgrowth. In the images above, cells with reduced levels of MKK7 mRNA (bottom) have curled and bent microtubules (red in merged, black in right panels), compared to control cells (top).

Daniel Feltrin, Ludovico Fusco, Harald Witte, Francesca Moretti, Katrin Martin, Michel Letzelter, Erika Fluri, Peter Scheiffele, & Olivier Pertz (2012). Growth Cone MKK7 mRNA Targeting Regulates MAP1b-Dependent Microtubule Bundling to Control Neurite Elongation PLOS Bio, 10 (12) : 10.1371/journal.pbio.1001439

August 10, 2012

Biologists are always looking for ways to push the limits of what our microscopes are capable of doing. These Microscopy Olympians (which should be a real thing, seriously) understand the physics and biology behind imaging cells in order to build, tweak, and test fancy-shmancy new technologies. And, just like the real Olympics, I watch from my couch with a bag of pretzels in front of me.

To accurately capture high resolution images of cells, biologists are always improving ways to capture three dimensional structures over time in a living cell. Combining nanoscale resolution with live imaging has proven a challenge, recently helped by a paper that describes the tweaks made to earlier microscopy setups. Paszek and colleagues presented their technique called scanning angle interference microscopy, in which dynamic cellular events and structures are imaged with nanoscale resolution in three dimensions. In the image above, microtubules imaged using this technique show their location in three dimensions. The “height” along each microtubule is color-coded (in nm) to show that microtubules bend down towards the cell cortex.

Paszek MJ, Dufort CC, Rubashkin MG, Davidson MW, Thorn KS, Liphardt JT, & Weaver VM (2012). Scanning angle interference microscopy reveals cell dynamics at the nanoscale. Nature methods, 9 (8), 825-7 PMID: 22751201

July 30, 2012

It may appear that chromosomes are just floating around inside of the nucleus, but that couldn’t be further from the truth. Inside that double membrane of the nucleus is a lot of chromosome choreography, and this is especially true during meiosis. Today’s image is from a paper showing the interaction between two nuclear envelope proteins and their regulation of chromosome dynamics and pairing.

Meiosis is a type of cell division that reduces the number of chromosomes down to one copy of each in the resulting daughter cells, called gametes (eggs and sperm). During meiosis, the pairing of homologous chromosomes (matching chromosomes) is important for recombination and chromosome segregation later in meiosis. Recombination is the exchange of DNA regions between two paired chromosomes, and is key in generating genetic variation. In yeast and worms, KASH domain proteins and SUN domain proteins of the nuclear envelope interact to ensure proper chromosome pairing and positioning within the nucleus. Mammals were known to have a SUN domain protein, SUN1, and a recent paper identified its KASH domain binding partner, KASH5. Morimoto and colleagues found that KASH5 and SUN1 both localize at telomeres, regions at the ends of chromosomes, during meiosis in mice. In addition, KASH5 interacts with the microtubule-associated dynein-dynactin complex to regulate chromosome movement. In the images above, chromosomes from mouse spermatocytes have both KASH5 and SUN1 localized at telomeres throughout meiosis (chromosomes are blue).

Akihiro Morimoto, Hiroki Shibuya, Xiaoqiang Zhu, Jihye Kim, Kei-ichiro Ishiguro, Min Han, & Yoshinori Watanabe (2012). A conserved KASH domain protein associates with telomeres, SUN1, and dynactin during mammalian meiosis originally published in the Journal of Cell Biology, 198 (2), 165-172 DOI: 10.1083/jcb.201204085

July 5, 2012

I’ve never run a marathon, but I’d imagine that it is a rollercoaster of feelings that finishes with a life “high” that is unbeatable. That’s how I feel when I read a paper from the journal Cell. They’re long, exhausting, sweat-inducing, and frequently some of the most rewarding paper-reading experiences a biologist can have. Today’s image is from a Cell paper that is so extensive in data, with a story that starts with protein localization and ends with a behavior study in mice.

Fibroblast growth factors (FGFs) are proteins that regulate several processes during development, such blood vessel growth and neurogenesis. A research group recently investigated the developmental role of FGF13, a growth factor believed to be connected to X-chromosome-linked mental retardation. Wu and colleagues found that FGF13 interacts with and stabilizes microtubules in cerebral cortical neurons during development. Through this interaction, FGF13 is required to polarize neurons—an event necessary for proper neuron migration and brain development. Finally, Wu and colleagues tracked the behavior of mice lacking FGF13, and found a reduced learning ability similar to that seen in X-chromosome-linked mental retardation patients. Images above show control (left) and FGF13-silenced (right) neurons in cerebral cortical slices. Without FGF13, neurons could not complete their radial migration in the tissue.

Wu QF, Yang L, Li S, Wang Q, Yuan XB, Gao X, Bao L, & Zhang X (2012). Fibroblast growth factor 13 is a microtubule-stabilizing protein regulating neuronal polarization and migration. Cell, 149 (7), 1549-64 PMID: 22726441

 Copyright ©2012 Elsevier Ltd. All rights reserved.

July 2, 2012

Microscopy can truly be a religious experience for some of us. We get to see the beauty of life unfold before our eyes, often in a dark room with the white-noise hum of equipment, all while being humbled by the mysteries in front of us. No matter your education, your amazing research pedigree, or the fancy-shmancy technology in front of you, you still don’t know how the heck it all happens…even in the tiniest of organisms. I’ll drink a bottle of immersion oil if that doesn’t bring your ass down a peg. Today’s image is from a paper describing the identification of a microtubule-like cytoskeleton in a bacteriophage.

Bacteriophages are viruses that infect bacteria. They are very common, found in dirt, sea water, and any place bacteria are found, and are very diverse. While bacteria are known to have cytoskeletal structures similar to our own cells, actin- or tubulin-like structures were not previously described in bacteriophages. A research group recently identified a tubulin-like protein called Phu-Z. Like the microtubules formed from tubulin in our own cells, Phu-Z assembles into filaments that surround the bacteriophage DNA and helps to position it within the infected bacterial cell. In the image above, Phu-Z is expressed in a bacterium and is able to assemble into filaments.

Kraemer JA, Erb ML, Waddling CA, Montabana EA, Zehr EA, Wang H, Nguyen K, Pham DS, Agard DA, & Pogliano J (2012). A Phage Tubulin Assembles Dynamic Filaments by an Atypical Mechanism to Center Viral DNA within the Host Cell. Cell, 149 (7), 1488-99 PMID: 22726436
Copyright ©2012 Elsevier Ltd. All rights reserved.

 

May 14, 2012

Transformers may have been the hot toy in the 80s and I definitely remember coveting my big brother’s collection, but they have nothing on the cool ability of cells to completely transform themselves. During epithelial remodeling, a polarized epithelial cell transforms itself into a migratory cell….they truly are “more than meets the eye” (“robots in disguise!” ptchoo ptchoo!). Today’s stunning images are from a paper describing the cytoskeletal changes that drive this transformation.

Epithelial remodeling is the transformation of an epithelial cell into a migratory cell, a process that occurs throughout development. Although it is known that dramatic cytoskeletal changes drive epithelial remodeling, it wasn’t previously understood how these changes occur in a three-dimensional tissue. Gierke and Wittmann recently used high resolution imaging of cultured 3D epithelial cysts to track cytoskeletal changes during morphogenesis. After triggering an epithelial-to-mesenchymal (migratory) transition in the cysts, Gierke and Wittmann found that the growth rate of microtubules increased prior to any visible changes in cell shape, and that microtubules reorganize and grow into cell extensions during epithelial remodeling. In addition, this microtubule reorganization requires the function of EB1, a protein that binds to the plus-end of growing microtubules and can regulate the interaction of microtubules with the cortex of the cell. The images above show cell extensions in cysts triggered to undergo an epithelial-to-mesenchymal transition (actin filaments are labeled). Control extensions (top row) continuously grow over time, with actin-rich lamellipodia at the tip. Without EB1 (bottom row), extensions lack a single actin-rich tip and instead have multiple protrusions that do not grow.

Gierke, S., & Wittmann, T. (2012). EB1-Recruited Microtubule +TIP Complexes Coordinate Protrusion Dynamics during 3D Epithelial Remodeling Current Biology, 22 (9), 753-762 DOI: 10.1016/j.cub.2012.02.069

 Copyright ©2012 Elsevier Ltd. All rights reserved

 

April 26, 2012

One of my favorite analogies in cell biology revolves around cupcakes and asymmetric cell division, which happen to be two of the most wonderful things in the world. If you cut a cupcake in half down the center, you have two equal pieces with both icing and cake. Or, you can cut the cupcake in half across the center, and have one piece with just icing and one piece with just cake. Today’s image is from a paper describing how a cell divides to result into two equal icing-and-cake cells.

During development, the orientation of cell division within an epithelial sheet helps to drive tissue shape changes. Symmetric cell division, during which the mitotic spindle is parallel to the plane of the sheet, leads to tissue growth and elongation, while asymmetric division, during which the spindle is perpendicular to the epithelial sheet, causes tissue thickening and stratification. Most research on mitotic spindle orientation has focused on asymmetric cell division, but a recent paper describes interesting results on how a spindle is positioned during symmetric division. Woolner and Papalopulu looked at epithelial tissue in early frog embryos to test possible mechanisms of spindle positioning in symmetric cell divisions. As seen in the image above (left), the spindle is positioned precisely in the plane of the epithelial sheet. Woolner and Papalopulu found that a basally-directed force (pushing down, into the sheet) is provided by microtubules and myosin-10, while an apically-directed force is provided by actin filaments and myosin-2. Both of these forces are required to position the spindle in the plane of the epithelium, and at its proper position along the apical-basal axis. In the middle image above, the spindle is positioned near the apical cell surface after astral microtubules were disrupted. After actin-filament disruption (right image), spindles moved toward the basal cell surface.

Woolner, S., & Papalopulu, N. (2012). Spindle Position in Symmetric Cell Divisions during Epiboly Is Controlled by Opposing and Dynamic Apicobasal Forces Developmental Cell, 22 (4), 775-787 DOI: 10.1016/j.devcel.2012.01.002

Copyright ©2012 Elsevier Ltd. All rights reserved.