November 29, 2010

Basic research is fundamental if we want to make strides in understanding disease. Please (politely) shout this from the mountaintops and make sure your lawmakers and funding agencies understand this. Today’s image is from a paper that investigates a key player in cell scattering, which is an event very similar to cancer metastasis.

Cell scattering is a term used to describe cell-cell dissociation and migration and occurs in liver development, organ regeneration, and metastasis. Cell scattering is induced by hepatocyte growth factor/scatter factor (HGF/SF1), and a recent paper describes similar cell scattering after a block to the protein α₅β₁ integrin, which is a receptor mediating the attachment of the cell to the surrounding extracellular matrix. In addition, blocking the function of this integrin triggers changes in expression of other proteins that mediate adhesion and migration. Image shows control (top) or integrin-blocked (bottom) liver progenitor cells. After a functional block to integrin function, cells are scattered and have decreased levels of E-cadherin (green), which is important in cell-cell adhesion of epithelial cells. Nuclei are in blue.

Vellón, L., Royo, F., Matthiesen, R., Torres-Fuenzalida, J., Lorenti, A., & Parada, L. (2010). Functional blockade of α5β1 integrin induces scattering and genomic landscape remodeling of hepatic progenitor cells BMC Cell Biology, 11 (1) DOI: 10.1186/1471-2121-11-81

Many thanks!

In order to celebrate Thanksgiving with my fellow Americans, I wanted to spend a moment expressing my thanks. I’m thankful for cells and microscopes. I’m thankful for emerging imaging techniques, lasers, and the physics that make it all possible. I’m thankful for beautiful dividing, migrating, and endocytosing cells. Most of all, I’m thankful for all of the amazing cell biologists who transform their own curiosities into amazing advances in our understanding.

Many thanks to the cell biologists who have given me their enthusiastic consent and support to blog about their precious images, and to the many journals that have granted me permission. Many thanks to all of my readers for letting me have fun totally geeking out over fantastic images!!

Now, I’ll go stuff myself with 15lbs of a Thanksgiving meal, watch some football, and try to explain to my toddler daughter why she can’t have the balloons seen in the Macy’s Thanksgiving Day Parade.

Next week, we’ll be back to some amazing images.

November 22, 2010

As cold and flu season rears its ugly head, it’s time for us to appreciate our immune systems and thank the researchers the help us understand it. Today’s image is a double-whammy—a cool microscopy technique and great science.

Germinal centers (GCs) are regions in our lymph nodes where B cell lymphocytes proliferate, produce antibodies, and undergo selection in order to stage an immune response against invaders. There are two regions within the GCs – the light zone and the dark zone – and a recent paper clarifies the different roles of these regions in B cell division and selection. Victora and colleagues used a photactivatable green fluorescent protein (PA-GFP) in germinal centers and photactivated certain regions of cells. By tracking the dynamics of the green fluorescent signal, they were able to understand the roles of the different regions within the GC. Image is of a mouse lymph node before (left) and after (right) photoactivation of a cleverly selected region (“GFP”).

BONUS!! Cool movies of photoactivated regions found here.

Victora, G., Schwickert, T., Fooksman, D., Kamphorst, A., Meyer-Hermann, M., Dustin, M., & Nussenzweig, M. (2010). Germinal Center Dynamics Revealed by Multiphoton Microscopy with a Photoactivatable Fluorescent Reporter Cell, 143 (4), 592-605 DOI: 10.1016/j.cell.2010.10.032
©2010 Elsevier Ltd. All rights reserved.

November 18, 2010

When you see the lovely images on the cover of a journal, you can be sure that those images are the tip of the iceberg for a cell biologist's “portfolio” of images. Today’s image complements the cover and accompanying paper in this month’s Journal of Biological Chemistry and deserves its own spotlight (yes, I’m referring to HighMag as a “spotlight”).

The myosin family of actin motors is large and diverse. One myosin, Myo3A, is found in the stereocilia of the inner ear and has an unconventional structure. Quintero and colleagues recently found that the kinase domain of Myo3a autophosphorylates the motor domain, which alters the localization of Myo3A and decreases the formation of actin protrusions called filopodia in cultured cells. The authors suggest that the function and localization of Myo3A in other bundled actin structures, like stereocilia, are regulated by this auto-inhibition mechanism. Image above shows the actin-binding protein espin (purple) and a mutant form of Myo3A that lacks the kinase domain (white) in a cultured cell.

Quintero, O., Moore, J., Unrath, W., Manor, U., Salles, F., Grati, M., Kachar, B., & Yengo, C. (2010). Intermolecular Autophosphorylation Regulates Myosin IIIa Activity and Localization in Parallel Actin Bundles Journal of Biological Chemistry, 285 (46), 35770-35782 DOI: 10.1074/jbc.M110.144360

November 15, 2010

Cell biologists make amazing discoveries using cells grown flat on culture dishes, yet the cells in an organism grow and function in three dimensions. Some cell biologists use clever tricks to understand how cells function in three dimensions by using cells cultured in gels, and they find out very valuable information.

Throughout biology there are many cases of oriented cell division, during which a cell orients the mitotic spindle on a specific axis. These cell divisions can occur throughout development in stem cell divisions, tissue morphogenesis, and epithelial sheet formation. Epithelial sheets are monolayers of polarized cells, and cells must divide within the plane of the sheet in order to maintain the monolayer. A recent paper uses cultured mammalian cells grown as cysts as a model for epithelial cell divisions, and describes the important role of a protein called Pins in ensuring that cell divisions are oriented correctly. Hao and colleagues found that the correct localization of Pins on the surface of epithelial cells is regulated by the Par3 and aPKC polarity proteins. Images above are of cysts with (left) or without (right) Par3. While the wild type cyst has one lumen facing the apical surface of cells (green), cysts without Par3 form multiple lumens.

Hao, Y., Du, Q., Chen, X., Zheng, Z., Balsbaugh, J., Maitra, S., Shabanowitz, J., Hunt, D., & Macara, I. (2010). Par3 Controls Epithelial Spindle Orientation by aPKC-Mediated Phosphorylation of Apical Pins Current Biology, 20 (20), 1809-1818 DOI: 10.1016/j.cub.2010.09.032
Copyright ©2010 Elsevier Ltd. All rights reserved.

November 11, 2010

As long there are cells and fascinated scientists, then there will always be unsolved mysteries. A recent paper helps clear up discrepancies in the actin literature, using a combination of killer microscopy and a systematic look at how one protein functions.

So many cellular processes depend on a dynamic network of actin filaments, and there is a long list of proteins that associate with and regulate these networks. One of those proteins is called VASP and is found at the leading edge of migrating cells in lamellipodia and filopodia. Recent work clarifies the different modes of VASP-actin filament binding and describes the mechanism by which VASP functions in actin filament assembly. Images show stabilized actin filaments (middle, green in merged) and single tetramers of VASP (top, orange in merged) bound to the side of these filaments.

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

Hansen, S., & Mullins, R. (2010). VASP is a processive actin polymerase that requires monomeric actin for barbed end association The Journal of Cell Biology, 191 (3), 571-584 DOI: 10.1083/jcb.201003014

November 8, 2010

I love microtubules, and I have friends that love actin. To keep the debate over coolest cytoskeletal element civil, I’m the diplomat that loves proteins that interact with both microtubules and actin.

During neuron development, one of the many protrusions coming from the cell body undergoes rapid growth to eventually become the axon, and the regulation of this process is complicated. The microtubule-associated protein MAP1B was previously known to play a role in axonal development, but a recent paper teases apart how MAP1B functions. The authors found that MAP1B regulates the cross-talk between the microtubule and actin cytoskeletons during axon growth. Images show wild type (left) and MAP1B-deficient (right) neurons: the wild-type neuron has only one long axon originating from the cell body, while the MAP1B-deficient neuron does not.

Reference: Carolina Montenegro-Venegas, Elena Tortosa, Silvana Rosso, Diego Peretti, Flavia Bollati, Mariano Bisbal, Ignacio Jausoro, Jesus Avila, Alfredo Cáceres, and Christian Gonzalez-Billault. Authors’ Molecular Biology of the Cell paper can be found here.

November 4, 2010

Back when I was a budding little scientist, I joined the first lab that showed me glowing cells in a whole living organism. It wasn’t a rule I made for myself and my research had nothing to do with those particular cells called seam cells, but I knew that a lab with glowing worms would be a cool place to be.

Seam cells are hypodermal cells that are aligned along the left and right sides of the worm C. elegans. They serve an important purpose in postembryonic development—after the worm hatches, seam cells undergo stem-cell-like divisions that produce several different types of cells. A recent paper describes the role of spindle checkpoint proteins, which ensure proper chromosome segregation during mitosis, in the postembryonic divisions of seam cells. When one of these checkpoint proteins, MDF-2 (Mad2), is missing, the number and alignment of seam cells is disrupted. Images above show seam cells (green) in normal (top) and mdf-2 mutant (bottom) worms. The mutant worms frequently have extra or clustered seam cells (box) instead of the ordered alignment seen in normal worms.

Reference: Maja Tarailo-Graovac, Jun Wang, Jeffrey SC Chu, Domena Tu, David L Baillie and Nansheng Chen. Authors’ BMC Cell Biology paper can be found here.

November 1, 2010

Microtubules are some of the most dynamic structures in a cell, and are simply mesmerizing to watch.

Microtubules serve numerous functions in a cell—they provide the main structure of the mitotic spindle and serve as tracks for transport within a cell. Microtubules are assembled by subunits of tubulin in a polarized fashion so there is a plus and minus end. This polarity is significant—plus ends are very dynamic and are the sites of the majority of action and dynamics, while minus ends are stabilized and anchored at the microtubule organizing center in most cells. A recent paper describes the identification of a protein called Patronin that stabilizes the minus ends of microtubules. In cells without Patronin, microtubules are not anchored and are found freely moving throughout the cytoplasm, as seen in the images above. In normal interphase cells (left), microtubules are anchored at nucleating sites, but in cells without Patronin (right), entire microtubules can be seen in the cytoplasm (arrows, inset).

Reference: Sarah S. Goodwin and Ronald D. Vale. Cell 143 (2), 263-274. ©2010 Elsevier Ltd. All rights reserved. Paper (and many cool movies!) can be found here.

BONUS!! Cool movie of above image can be found below!