April 17, 2014

The endoplasmic reticulum and humans have quite a bit in common. Both are dynamic and constantly changing, but both also need something to ground and stabilize them. Maybe I’m reading too much into the beauty of the ER, but the image today is from a paper that only fuels my fascination.

The endoplasmic reticulum (ER) is a large, complex membrane-bound organelle that spreads throughout the cell and hosts the synthesis, folding, and sorting of membrane and secretory proteins. This network is dynamic and constantly rearranging, with diverse structural and functional domains. A recent paper describes the investigation into the role of the actin cytoskeleton in regulating ER sheet persistence and maintenance, which is important as the stationary domain of the ER. Joensuu and colleagues identified a subset of actin filaments associated with the ER, specifically to polygons defined by ER tubules and sheets. Actin depolymerization caused ER sheet fluctuation and resulted in a defective ER network. The actin motor myosin 1c also localizes to these actin filament arrays. In the images above, actin filament arrays (magenta, arrows) localize to the polygons (asterisks) associated with the ER (green).

Joensuu, M., Belevich, I., Ramo, O., Nevzorov, I., Vihinen, H., Puhka, M., Witkos, T., Lowe, M., Vartiainen, M., & Jokitalo, E. (2014). ER sheet persistence is coupled to myosin 1c-regulated dynamic actin filament arrays Molecular Biology of the Cell, 25 (7), 1111-1126 DOI: 10.1091/mbc.E13-12-0712

April 10, 2014

When you host a party at your home, do you hire a caterer to bring in food or do you cook the food right there in your kitchen? One of these options leaves a lot more wiggle room for last-minute changes—a few extra guests, a gluten allergy, a pregnant lady with a disgust for wobbly desserts. A cell recognizes this distinction too. When making certain proteins, a cell will synthesize proteins where and when they’re needed. Today’s image is from Natasha Gutierrez, who recently published a study describing the role of β-actin mRNA and monomer synthesis in adherens junction assembly.

The actin cytoskeleton is made of actin filaments and countless actin-regulating proteins that guide the ever-changing dynamics of the cytoskeleton. Actin filament polymerization is regulated by localized synthesis of β-actin monomers from β-actin mRNA. A recent paper by Gutierrez and colleagues shows that the assembly of adherens junctions (AJs), epithelial cell-cell adhesion structures, requires localized β-actin monomer synthesis, the β-actin 3’ UTR and β-actin mRNA zipcode sequence at cell-cell contact sites. Additionally, active RhoA, which targets zipcode-mediated β-actin mRNA localization, is localized to cell-cell contact sites. In the unpublished images above, mammalian cells were treated with increasing levels (top to bottom) of a Rho inhibitor. The ability to form AJs, seen as the colocalization of actin filaments (left, green in merged) and E-cadherin (middle, red in merged) at cell-cell contact sites, decreased with increasing levels of the Rho inhibitor.

Gutierrez, N., Eromobor, I., Petrie, R., Vedula, P., Cruz, L., & Rodriguez, A. (2014). The B-actin mRNA zipcode regulates epithelial adherens junction assembly but not maintenance RNA DOI: 10.1261/rna.043208.113

April 2, 2014

Nuclear envelope breakdown is far prettier than my own breakdown when I realized that Girl Scout “cookie season” is over. Today’s image is from a paper that describes the importance of SUN proteins in nuclear envelope breakdown.

Early in mitosis, a cell’s nuclear envelope breaks down to allow the attachment of chromosomes to the mitotic spindle. Nuclear envelope breakdown (NEBD) depends on a tearing process, during which microtubules pull the nuclear envelope towards the centrosomes. Turgay and colleagues found that the SUN proteins help to clear membranes from chromatin during NEBD. SUN proteins reside in the inner nuclear membrane and are part of a complex that connects the nucleus to the cytoskeleton. As seen in the images above, simultaneous depletion of both SUN1 and SUN2 (bottom timelapse) delayed removal of the nuclear envelope (green; chromosomes in red), when compared to control (top).  

Turgay, Y., Champion, L., Balazs, C., Held, M., Toso, A., Gerlich, D., Meraldi, P., & Kutay, U. (2014). SUN proteins facilitate the removal of membranes from chromatin during nuclear envelope breakdown The Journal of Cell Biology, 204 (7), 1099-1109 DOI: 10.1083/jcb.201310116

March 27, 2014

You might think of your bones as unchanging, but they are far more dynamic than you think. Today’s image is from a paper identifying a new blood vessel subtype found in the mouse skeletal system.

Osteogenesis is the formation of new bone tissue, and is important in bone renewal and fracture healing. Recent work suggests that osteogenesis may depend on the presence of blood vessels. A recent paper identified a new capillary subtype found in the mouse skeletal system. Kusumbe and colleagues found that these microvessels mediate growth of bone vasculature, and couple osteogenesis with angiogenesis (the formation of new blood vessels). These vessels and their associated osteoprogenitors were reduced in older bone, yet the reversal of this decline allowed bone mass renewal. In the images above, the microvessels (green) have a branched organization in a juvenile mouse tibia (arrowheads point to interconnections).

Kusumbe, A., Ramasamy, S., & Adams, R. (2014). Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone Nature, 507 (7492), 323-328 DOI: 10.1038/nature13145
Adapted by permission from Macmillan Publishers Ltd, copyright ©2014

March 19, 2014

Migration fingers are the spirit fingers of a migrating epithelial sheet of cells. Woowoo!! Today’s image is from a cool paper on the forces exerted by a migration finger, so naturally I’m showing my enthusiasm with my own spirit fingers.

Cells can migrate on their own or as part of an epithelial sheet of many cells. Collective migration features the forward movement of multicellular migration fingers, and can be seen throughout development, in spreading tumors and in healing wounds. The formation of each migration finger begins with the transformation of a single cell into a leader cell. A recent paper looks at leader cells and migration fingers, specifically the biochemical mechanisms involved and the generation of forces exerted by migration fingers. Reffay and colleagues monitored the traction forces exerted by a migration finger, and found that the leader cell exerts a large mechanical force that drags its followers with the help of the small GTPase RhoA. In the images above, the contractile acto-myosin cable that runs the length of the migration finger is cut by laser photoablation (arrow, middle). A new leader cell is formed at the site of the cut (asterisk, right), suggestion that the cable serves to prevent the formation of new leader cells, which in turn allows the formation of long migration fingers.


Reffay, M., Parrini, M., Cochet-Escartin, O., Ladoux, B., Buguin, A., Coscoy, S., Amblard, F., Camonis, J., & Silberzan, P. (2014). Interplay of RhoA and mechanical forces in collective cell migration driven by leader cells Nature Cell Biology, 16 (3), 217-223 DOI: 10.1038/ncb2917
Adapted by permission from Macmillan Publishers Ltd, copyright ©2014

March 12, 2014

I love a lot of things that are rings, especially donuts. Turns out, though, that ring chromosomes are terrible news. A recent paper shows the loss of ring chromosomes when cells are reprogrammed, suggesting possible ‘chromosome therapy’ through cell reprogramming.

Ring chromosomes form when the two arms of a chromosome fuse, and are sometimes associated with large terminal deletions. These ring chromosomes lead to birth defects, mental disabilities, and growth retardation. Unfortunately, there are no treatments for ring chromosome disorders due the severity of the aberrations. In a recent study, Bershteyn and colleagues generated induced pluripotent stem cells (iPSCs) from cells of a Miller Dieker Syndrome patient with large deletions on ring chromosome 17. The induced stem cells lost the ring chromosome and duplicated the normal homologous chromosome through a mechanism called compensatory uniparental disomy. The images above show two karyotypes—one with the ring chromosome 17 (left, inset), and one without (right).

Bershteyn, M., Hayashi, Y., Desachy, G., Hsiao, E., Sami, S., Tsang, K., Weiss, L., Kriegstein, A., Yamanaka, S., & Wynshaw-Boris, A. (2014). Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells Nature, 507 (7490), 99-103 DOI: 10.1038/nature12923
Adapted by permission from Macmillan Publishers Ltd, copyright ©2014

March 5, 2014

Mitochondria are the cellular power plants, but bigger power plants are not always a good thing. Defects in the regulation of mitochondrial size and dynamics can cause neurodegenerative diseases such as Alzheimer’s disease. Today’s image is from a paper describing an important player in mitochondrial division, or fission.

Mitochondria serve as the cellular power plants due to their production of ATP, the cell’s energy source, and are quite dynamic, with fusion and fission events occurring regularly. Mitochondrial fission is how mitochondria divide, but fission also plays an important role in apoptosis and ridding the cell of damaged mitochondrial components. In current models of fission, the GTPase dynamin (Drp1) forms a ring around and constricts the mitochondrial membranes. A recent paper describes the importance of the myosin II, an actin motor, in Drp1-mediated fission. Korobova and colleagues found that inhibition of myosin II resulted in abnormally long mitochondria. This inhibition of myosin II also affected the presence of Drp1 at mitochondria. In the images above, the use of blebbistatin, a myosin II chemical inhibitor, resulted in long mitochondria (right), compared to control mitochondria (left).

Korobova, F., Gauvin, T., & Higgs, H. (2014). A Role for Myosin II in Mammalian Mitochondrial Fission Current Biology, 24 (4), 409-414 DOI: 10.1016/j.cub.2013.12.032
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