HighMag

May 7, 2012

Phosphorylation serves as a molecular switch, and the combinations of different proteins phosphorylated or dephosphorylated at any given time is mind-numbing. Phosphorylation caused one of many “Holy crap, cells are amazing!” moments in college as I realized how the regulation within a cell can be so complex. Today’s image is from a study that looks at the regulation of phosphorylation of a polarity protein.

Protein kinase C (PKC) is a family of kinases, one of which is the well-studied polarity protein atypical PKC (aPKC). These kinases must be phosphorylated before their catalytic domain is activated. The protein PDK1 serves to phosphorylate and activate newly-made PKC proteins, and a recent paper reveals that it can also phosphorylate older PKC proteins that have been since dephosphorylated, seen as a “rescue” of activity. Mashukova and colleagues also found that PDK1 is localized in membrane compartments on the apical side of some epithelial cells in close proximity to intermediate filaments, suggesting a new signaling function in these membrane compartments (endosomes). In the images above, epithelial cells have PDK1 (red) localized to the apical pole of the cells, where intermediate filaments (green) are found.

Mashukova, A., Forteza, R., Wald, F., & Salas, P. (2012). PDK1 in apical signaling endosomes participates in the rescue of the polarity complex atypical PKC by intermediate filaments in intestinal epithelia Molecular Biology of the Cell, 23 (9), 1664-1674 DOI: 10.1091/mbc.E11-12-0988

May 3, 2012

Where did you come from? Understanding the answer to this question helps you get a grasp on who you are currently, and who you are becoming. Whoa, that was deep…enough of that crap! A recent paper puts the psychotherapy treatment on cells in the developing heart and adds to our understanding of where they are from.

The change that takes place in a developing heart is astounding—a simple tube structure with a single layer of cardiac muscle cells called cardiomyocytes must develop into a complex adult structure. How the early cardiomyocytes divide and move around to form the adult heart is difficult to map out due to their dynamic behavior and their location in a tissue that is difficult to image. A recent paper describes the use of a recently-developed technology called Brainbow, in which different cells can be labeled with about 90 different colors. Using Brainbow techniques, Gupta and Poss were able to track the division and movement of individual cardiomyocytes in the developing zebrafish heart, and found that the cells expand the cardiac tissue in patches of various sizes and shapes. By using clonal dominance as a mechanism for tissue expansion, the process is reminiscent of stem cells. The image above shows the surface of the ventricular side of a developing heart, each color representing a different clonal patch that arose from a single cardiomyocyte.

Gupta, V.; Poss, K. (2012). Clonally dominant cardiomyocytes direct heart morphogenesis Nature, 484 (7395), 479-484 DOI: 10.1038/nature11045

April 30, 2012

One might think that once you’ve won your first Nobel Prize, it’s time to kick back and watch the youngsters do the dirty work of solving all of biology’s riddles. No so. Apparently, Nobel-ers don’t like to kick back at all, but continue to push the limits of our knowledge. I think they’re all wearing superhero capes underneath their biologist uniforms (plaid shirts and old jeans?). Today’s image is from the lab of Eric Wieschaus, in a paper that provides a fascinating alternative mechanism to the prevailing model of epithelial folding.

During development, groups of cells are shaped into tissues and organs in a process called morphogenesis. One of the earliest morphogenesis events is gastrulation, during which the embryo is organized into the three germ layers that will each develop into different tissues and organs. During gastrulation in the fruit fly, the dorsal side of the embryo undergoes two epithelial folds, the anterior and posterior dorsal transverse folds, at precise locations on the embryo. The current model of epithelial folding involves actin-myosin contractions that trigger the initial cell shape changes. Wang and colleagues recently found an alternative mechanism that underlies epithelial folding during fruit fly gastrulation. Specifically, Wang and colleagues found that the adherens junctions that form between epithelial cells relocate to more basal locations in the cells that initiate epithelial folding. The movement of adherens junctions, and in turn dorsal fold initiation, depends on the activity of the polarity proteins Bazooka and Par-1. In the images above, the initiation of anterior (pink arrow) and posterior (blue arrow) folds are visualized by high resolution live imaging. The localization of E-cadherin (white), a key adherens junction protein, drops from the apical surface (top of the cells) to a more basal location in the cells undergoing shape changes.

Wang, Y., Khan, Z., Kaschube, M., & Wieschaus, E. (2012). Differential positioning of adherens junctions is associated with initiation of epithelial folding Nature, 484 (7394), 390-393 DOI: 10.1038/nature10938

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

April 23, 2012

I love plants. I support our local botanical garden, I’ve been a vegetarian for almost 17 years, and I talk to (and hug) our yard’s new trees to welcome them to the family. Clearly I’m pro-plants. So why aren’t there more plant cell biology pictures on my blog? I have no excuses. Today, enjoy this lovely image from Arabidopsis, the go-to model plant in cell biology.

Rapid growth in a developing organism can provide challenges for the tissue, especially in tissues where the cells adhere to each other as they do in plants. In a developing plant, this rapid growth combined with differences in cell growth throughout the tissue causes mechanical strain and stress on the cells. A recent paper describes how katanin, a microtubule severing protein, is key in allowing the cells to respond to mechanical stress in the plant Arabidopsis. In this paper, Uyttewaal and colleagues imaged cell growth the in the plant’s stem cell niche, the shoot apical meristem, and found heterogeneity in the cell growth rates. Katanin mutants, however, had decreased growth variability in this same tissue. In normal plants, cortical microtubule arrays arrange themselves toward the regions of high mechanical stress, and this in turn affects growth. Uyttewaal and colleagues found that this directional arrangement of microtubule arrays is affected in katanin mutants, as seen in the images above. Images show shoot apical meristem tissue with microtubule arrays fluorescently tagged in green and their orientation marked in red. Microtubule arrays in wild type tissue (left) have a circumferential orientation in the peripheral zone (bottom, zoomed), while microtubule arrays in katanin mutants lacked a similar pattern (right images).

Uyttewaal, M., Burian, A., Alim, K., Landrein, B., Borowska-Wykręt, D., Dedieu, A., Peaucelle, A., Ludynia, M., Traas, J., Boudaoud, A., Kwiatkowska, D., & Hamant, O. (2012). Mechanical Stress Acts via Katanin to Amplify Differences in Growth Rate between Adjacent Cells in Arabidopsis Cell, 149 (2), 439-451 DOI: 10.1016/j.cell.2012.02.048
Copyright ©2012 Elsevier Ltd. All rights reserved.

April 19, 2012

“Location, Location, Location!” My husband and I have been watching too many house-hunting shows on HGTV (International Househunters FTW!), so the importance of location has been beaten into my brain. This real estate mantra applies in cell biology too. Today’s image is from a paper describing how the location of a dendrite can affect the strength of the synapse.

The synapse is the site of exchange between one neuron and another. The presynaptic terminal of a neuron’s axon will connect with, and send a signal to, the dendrite of another neuron. That dendrite is likely one of several that arise from the cell body of a neuron. A recent paper describes the relationship between the strength/function of the presynaptic terminal and the position of the dendrite, in certain neuron populations. According to de Jong and colleagues, the closer a dendrite is positioned to its own cell body, the higher the presynaptic strength of the axon connecting to it. In the images above, a cultured hippocampal neuron was stained for a marker of synaptic vesicles (left, green). The presynaptic strength was analyzed by the intensity of the synaptic vesicle staining and then color coded (middle), while the location of each synapse was measured as the distance from the cell body (right).

de Jong, A., Schmitz, S., Toonen, R., & Verhage, M. (2012). Dendritic position is a major determinant of presynaptic strength originally published in the Journal of Cell Biology, 197 (2), 327-337 DOI: 10.1083/jcb.201112135

April 16, 2012

I’m a homebody. I admit it. We’re all supposed to be adventurous, live on the edge, blah blah blah….but I thrive at home with my family around me. Maybe this makes me more like a stem cell than you glamorous jet-setters out there, and that seems pretty okay to me. Stem cells must stay in their niche, and a recent paper shows how some stem cells in the fruit fly do this through regulation of asymmetric division.

When adult stem cells divide, they produce a daughter cell that will take on a specific cell fate and another stem cell. To maintain this stem cell identity a stem cell must stay within its niche, or its microenvironment. In the fruit fly testes, germline stem cells (GSCs) stay adjacent to the “hub” within their niche and divide asymmetrically. In these divisions, a centrosome is positioned near the hub-GSC interface, and this aligns the mitotic spindle perpendicular to the hub. After cell division, the daughter cell that will remain a stem cell maintains its hub-GSC interface, while the differentiating cell is positioned further away. A recent paper shows that poor nutrient conditions prevent proper centrosome positioning in GSCs, which causes a delay in cell division via the centrosome orientation checkpoint. Roth and colleagues show that centrosome orientation is regulated by the insulin receptor pathway through its effect on the localization of Apc2, a cortical anchor for GSC centrosomes. The image above shows GSCs surrounding the hub (star) in a fruit fly testes cultured in poor nutrient conditions. One cell has correct centrosome orientation (yellow circle, centrosomes are red dots), while two cells (white circle) have misoriented centrosomes (arrowheads).

BONUS! Aren't GSCs pretty!? Check out these other posts on GSCs (here and here) that I wrote last week.

Roth, T., Chiang, C., Inaba, M., Yuan, H., Salzmann, V., Roth, C., & Yamashita, Y. (2012). Centrosome misorientation mediates slowing of the cell cycle under limited nutrient conditions in Drosophila male germline stem cells Molecular Biology of the Cell, 23 (8), 1524-1532 DOI: 10.1091/mbc.E11-12-0999