HighMag

June 7, 2012

Al Green was most likely singing “Let’s Stay Together” to some babe he was in love with, but I’d like to imagine he was talking about cells. I’m not sure they play Al Green in the lab that today’s image comes from, but I’d suggest adding his work to their playlist (good advice for everyone, really). Today’s image is from a paper showing how cadherin’s structural changes affect cell adhesion.

Cadherins are transmembrane proteins that play an important role in cell-cell adhesion. Cell adhesion is a dynamic process that is highly regulated throughout development, during cancer progression, and for basic tissue function. A recent paper shows how physical and structural changes in certain cadherin domains affect the adhesive state of that cadherin. In this paper, Petrova and colleagues used a human colorectal tumor line of cells that don’t normally adhere to one another, but can be triggered to adhere and compact. By using a set of specialized monoclonal antibodies that can bind to certain states of active or inactive cadherin domains, Petrova and colleagues found that the structural changes in regions near calcium-binding sites, mediated by changes in another adhesion player called p120-catenin, affect adhesion activation. In the images above, cells treated with a control antibody (left) remain round and unattached, while cells treated with an adhesion-activating antibody (right) became attached and compact.

Petrova, Y., Spano, M., & Gumbiner, B. (2012). Conformational epitopes at cadherin calcium-binding sites and p120-catenin phosphorylation regulate cell adhesion Molecular Biology of the Cell, 23 (11), 2092-2108 DOI: 10.1091/mbc.E11-12-1060

June 4, 2012

If you’re like me, you look forward to summer’s juicy blueberries. You’ll sprinkle or mix them into everything you eat, and sneak a big handful every time you open your fridge. You tell yourself that it’s all for the antioxidants. Just make a bigger rationalization leap and say you’re helping blueberries fight alongside dividing mitochondria to protect us from the evils of oxidative damage.

Mitochondria are the cell’s main source of energy, and without their dynamic dividing and fusing a cell can suffer. Neurological diseases such as Alzheimer’s, Parkinson’s, and Huntington’s are all associated with defects in mitochondrial division and fusion. A recent paper describes how mitochondrial division helps to protect neurons from oxidative damage, and in turn protects them from neurodegeneration. Kageyama and colleagues looked at postmitotic neurons in mice lacking Drp1, a protein that mediates mitochondrial division. In these neurons lacking Drp1, mitochondria extended into large tubules because of excess fusion, and showed an accumulation of oxidative damage and eventual neurodegeneration. This cell death could be reversed after application of antioxidants. The images above show Purkinje neurons in brain sections from 1, 3, and 6 month old mice (boxed areas show magnified images). Compared with control brain sections (top), Purkinje neurons lacking Drp1 (bottom) experienced dramatic neurodegeneration (90% of cells lost by 6 months).

Kageyama, Y., Zhang, Z., Roda, R., Fukaya, M., Wakabayashi, J., Wakabayashi, N., Kensler, T., Reddy, P., Iijima, M., & Sesaki, H. (2012). Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage originally published in the Journal of Cell Biology, 197 (4), 535-551 DOI: 10.1083/jcb.201110034

May 31, 2012

I love it when things really throw me for a loop. Like when I heard that Kim Kardashian earned a perfect SAT score and was accepted into Harvard. Okay, that’s not really true…but just imagine our collective “whaaaa?!” In science there are always things that flip your lid, and today’s image is from a paper that does just that. Clathrin-coated pit closure just got more interesting.**

Clathrin-mediated endocytosis is a process during which material is brought into the cell through pits coated with a clathrin lattice, which provides structure to the developing vesicle. Electron microscopy images of clathrin-coated pits show great detail about their structure, but can only provide snapshots of what occurs inside of the cell. A recent paper describes clathrin-coated pit closure using a technique that combines the imaging of structural detail seen in electron microscopy (in this case, called scanning ion conductance microscopy) with live confocal microscopy used to track fluorescently-tagged proteins. During conventional clathrin pit closure, the pit is closed and cleaved from flat membrane sheets. Shevchuk and colleagues, however, found that 70% of pits close using an alternative mechanism. In this mechanism, a membrane protrusion grew from one side of the clathrin pit and covered the pit to close it, as seen in the images above.

**Halvsies if this tagline prompts next summer’s blockbuster movie.

Shevchuk, A., Novak, P., Taylor, M., Diakonov, I., Ziyadeh-Isleem, A., Bitoun, M., Guicheney, P., Lab, M., Gorelik, J., Merrifield, C., Klenerman, D., & Korchev, Y. (2012). An alternative mechanism of clathrin-coated pit closure revealed by ion conductance microscopy originally published in the Journal of Cell Biology, 197 (4), 499-508 DOI: 10.1083/jcb.201109130

May 21, 2012

Whenever we go on a trip, my long-suffering husband quietly puts our luggage next the car and slinks away, trembling and twitching. He knows a mad-woman is ready to pack the trunk, playing luggage-Tetris until it all fits and speaking in tongues. Seriously, though, I’m freaking awesome. That said, I don’t envy the insane packing that a cell must accomplish to jam all of that DNA into neat little chromosomes ready for their own cell division road trip. A recent paper helps us understand how that happens at the centromere.

Centromeres are the regions on chromosomes that bind sister chromatids together and serve as the sites of kinetochore assembly during mitosis. The presence of the protein CENP-A is a hallmark of centromere location, as it is a histone H3 variant that helps package and compact centromeric DNA. It was previously presumed that CENP-A was passed down to daughter cells epigenetically, inherited from previous cell divisions, but a recent paper shows that this is not the case in the nematode worm C. elegans. According to Gassmann and colleagues, pre-existing CENP-A is not required for CENP-A localization to centromeres in subsequent divisions. In fact, CENP-A is unloaded from centromeres at one point in oogenesis, the production of eggs, and later reloaded onto centromeres. By mapping the location of CENP-A in the genome, Gassmann and colleagues found that regions of transcribed genes are regions where CENP-A is excluded, a pattern that changes when germline gene transcription switches to embryonic gene transcription. In the images above, the C. elegans germline is labeled to show chromosomes (top image) and the location of CENP-A (bottom). CENP-A is lost from chromosomes during the pachytene stage of meiosis and later reloaded onto chromosomes during diplotene, and is not found in sperm.

Gassmann, R., Rechtsteiner, A., Yuen, K., Muroyama, A., Egelhofer, T., Gaydos, L., Barron, F., Maddox, P., Essex, A., Monen, J., Ercan, S., Lieb, J., Oegema, K., Strome, S., & Desai, A. (2012). An inverse relationship to germline transcription defines centromeric chromatin in C. elegans Nature, 484 (7395), 534-537 DOI: 10.1038/nature10973
Adapted by permission from Macmillan Publishers Ltd, copyright ©2012

May 17, 2012

Hit the road, Jack! Cells undergo cell death all the time, but it’s important for a tissue to clear these cells out before problems crop up. Today’s image is from a paper showing the migration of apoptotic cells, and revealing the role a protein called elmo1 in cell corpse clearing.

Apoptosis is programmed cell death, and is as part of normal development and tissue function as cell division is. Apoptotic cells must be cleared out of the healthy tissue, and failure to do so can result in inflammation and autoimmunity. A recent paper describes the clearance of apoptotic cells in the developing brain of zebrafish, using real-time microscopy to track apoptotic cells. van Ham and colleagues found that apoptotic cells are able to migrate to the periphery of the tissue to contribute to their own removal, and use their own actin cytoskeleton to do so. Later in development, cell corpses are engulfed by large macrophage cells with the help of a protein called elmo1, a protein known to play a role in cell engulfment in other tissues. In the images above, a cell in the process of undergoing apoptosis migrates through the neural tube of a zebrafish embryo.

van Ham, T., Kokel, D., & Peterson, R. (2012). Apoptotic Cells Are Cleared by Directional Migration and elmo1- Dependent Macrophage Engulfment Current Biology, 22 (9), 830-836 DOI: 10.1016/j.cub.2012.03.027
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

May 10, 2012

I’m an old fart…heck, I was born an old fart. So, you won’t be seeing me in da club. But if I ever go, I’ll be reassured knowing that bouncers kick the knuckleheads out and keep the crowd to a safe limit. Though they may be beefy tough guys, bouncers are clearly getting their cues from epithelial cells, which extrude both dying and healthy cells when overcrowded, according to a recent paper.

Cell extrusion is the process in which epithelial cells get rid of apoptotic, or dying, cells. By getting rid of dying cells, the epithelial sheet can maintain its tight barrier function for the tissue or organ. A recent paper shows that epithelial sheets can also extrude healthy, living cells. According to Eisenhoffer and colleagues, an epithelial sheet overcrowded with cells will extrude living cells in order to maintain tissue homeostasis. This mechanism was found in human, canine, and zebrafish epithelial cells, and could be induced by overcrowding epithelial cells in a stretched, then released, chamber in the lab. Cells are extruding in the images of human colon epithelial tissue above. A dying cell in the process of extruding (right) shows caspase-3 staining (green, arrow), a marker for apoptosis, while a living cell extruding (left, arrowhead) does not.

Eisenhoffer, G., Loftus, P., Yoshigi, M., Otsuna, H., Chien, C., Morcos, P., & Rosenblatt, J. (2012). Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia Nature, 484 (7395), 546-549 DOI: 10.1038/nature10999