Happy Holidays, and Happy New Year!
We know so much information about cells by the amazing researchers that study how cells function in culture. It is always refreshing to see some biologists take this knowledge into a three-dimensional organism to help us understand even more about cells and development. It is even better when we get to see the images!
During development of an organism, cells frequently have to migrate from the spot where they were born to the spot where they will eventually form tissue and organs. Migration is a complicated process, and a recent paper describes the importance of the interaction between the plasma membrane and the cytoskeletal network directly underneath in order for migration to happen smoothly. The images above show three different types of membrane protrusions (blebs, filopodia, and lamellapodia) seen in prechordal plate progenitor cells in zebrafish embryos as they migrate to their eventual destination.
BONUS!! Check out a cool movie of the cell migration here.Diz-Muñoz, A., Krieg, M., Bergert, M., Ibarlucea-Benitez, I., Muller, D., Paluch, E., & Heisenberg, C. (2010). Control of Directed Cell Migration In Vivo by Membrane-to-Cortex Attachment PLoS Biology, 8 (11) DOI: 10.1371/journal.pbio.1000544
It is natural to hypothesize that similar processes in the cell may use the same proteins to do the job. So, it is very satisfying to the scientists who identify these proteins and add another piece to the cellular puzzle.
Lysosomes are organelles that break down the cell’s waste material, which reach lysosomes from a few pathways. Endocytosis is the uptake of material from the outside surface of the cell, and this material gets shuttled through different vesicles, some of which lead to lysosomes. Authophagy is the process in which a cell’s own components are transported to lysosomes in double-membrane vesicles for degradation. A recent paper identifies the mechanism of two proteins, called Rubicon and PLEKHM1, that play a role in both endocytosis and authophagy through their interaction with Rab7, a well-known small GTPase that is found on both late endosomes and lysosomes. Images show endosomes (left column, green in merged) and PLEKHM1 (middle column, purple in merged) with different Rab7 mutants. In cells with wild-type Rab7 or a Rab7 QL mutant, PLEKHM1 was localized to endosomes (white in merged indicates colocalization). In the dominant-negative Rab7 TN mutant, PLEKHM1 could not localize to endosomes.Tabata, K., Matsunaga, K., Sakane, A., Sasaki, T., Noda, T., & Yoshimori, T. (2010). Rubicon and PLEKHM1 Negatively Regulate the Endocytic/Autophagic Pathway via a Novel Rab7-binding Domain Molecular Biology of the Cell, 21 (23), 4162-4172 DOI: 10.1091/mbc.E10-06-0495
It is always exciting to read a paper that describes a fascinating discovery. It is even more exciting when that discovery opens the door to so many interesting questions. The paper that brought us today’s image is a great example of this.
When biologists look at cells growing on a culture dish, the cells are usually rounded blobs. Recently, a group of cell biologists had cells grow along lines in a culture dish to examine cell elongation. Regardless of cell size, all of the cells reached similar lengths. The intrinsic “ruler” that limits the length is a population of dynamic microtubules that grow along the side of the cell during elongation, and the authors suggest that this mechanism may play a large role during development. Images show microtubules in a control cell (left) and cells grown along an adhesive line (right) at different time points after attachment. The microtubules in the elongating cells become polarized and grow along the long sides of the cells.Picone R, Ren X, Ivanovitch KD, Clarke JD, McKendry RA, & Baum B (2010). A polarised population of dynamic microtubules mediates homeostatic length control in animal cells. PLoS biology, 8 (11) PMID: 21103410
Zebrafish is a freshwater fish that serves as a great model organism to cell and developmental biologists. During development, cells undergo dramatic reorganization during formation of the central nervous system, a process called neurulation. A recent paper describes the interaction between two proteins, called Protocadherin-19 and N-cadherin, and how these two proteins regulate cell movements during neurulation. These proteins together regulate cell-cell adhesion at a time when cells converge together to form a midline seam in the neural plate, a key feature of brain development. Images above are cell trajectories taken from time-lapse series of zebrafish embryos undergoing neurulation. The trajectories of cells in a normal embryo (top left) show a convergence of cells to the midline and a general movement of cells in one direction. Cells showed compromised movement in embryos with low levels of either protocadherin-19 (top, right), N-cadherin (bottom, left), or both (bottom, right).
BONUS!! Cool movies of two-photon image sequences can be found here.
Pathogens use some pretty awesome tricks in order to replicate in and infect cells. Today’s image is of a bacterial pathogen that exploits the actin cytoskeleton in its host cell.
Rickettsia are bacterial pathogens, and many Rickettsia species are able to co-opt its host cell’s actin cytoskeleton for its own motility within and between cells during infection. Rickettsia assemble “comet tails” that are made of parallel actin filament arrays, and these structures propel them in the direction they need to go. A recent paper found that a bacterial protein called Sca2 promotes actin filament assembly, and is found on the surface of the bacteria. Images above show Rickettsia in cell extracts with Sca2 (white or green) and actin (white or purple) labeled. Zoomed images (bottom) are of the bacterium in the lower left hand corner (top).
Adapted by permission from Macmillan Publishers Ltd, copyright 2010.Haglund CM, Choe JE, Skau CT, Kovar DR, & Welch MD (2010). Rickettsia Sca2 is a bacterial formin-like mediator of actin-based motility. Nature cell biology, 12 (11), 1057-63 PMID: 20972427
Centrosomes are the main microtubule organizing centers in a cell, and their position is crucial in processes such as mitosis, cell migration, and cell differentiation. During cell migration, centrosomes are positioned in front of the nucleus, facing the leading edge of the cell, and help maintain a polarized cytoskeleton. A recent paper describes how polarity proteins and the microtubule motor dynein function at the leading edge of crawling cells in order to regulate centrosome position. The images above highlight a microscopy technique called TIRF (total internal reflection fluorescence) microscopy, in which only shallow regions of the cell are illuminated and imaged, just above the glass coverslip where they are crawling in this case (crawling towards dotted line). In these images, microtubules (middle, red) are found at the very leading edge of the crawling cell (whole cell is top, green).
BONUS!! Cool movies of crawling cells here.
Manneville, J., Jehanno, M., & Etienne-Manneville, S. (2010). Dlg1 binds GKAP to control dynein association with microtubules, centrosome positioning, and cell polarity Originally published in The Journal of Cell Biology, 191 (3), 585-598 DOI: 10.1083/jcb.201002151
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
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.
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.
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