May 26, 2011

“Bring out yer dead!” Thankfully, epithelial sheets have a much more efficient and beautiful way of clearing out dying cells than the famous Monty Python scene. Today’s stunning images are from a paper describing the signaling epithelial cells use to push out dying cells. It’s no wonder that the authors’ image made the cover of Journal of Cell Biology!

The function and health of an organ strongly depends on the integrity of the epithelial sheet protecting it. In order to preserve the epithelial barrier, dying cells are pushed out of the epithelial sheet in a precise and finely-tuned process called apoptotic cell extrusion. In this event, cells surrounding the dying, apoptotic cell form an actin and myosin ring that contracts to push the dying cell out of the sheet. A recent paper describes the signaling that takes place to initiate cell extrusion. The dying cell produces a signal called bioactive lipid sphingosine-1-phosphate (S1P), which activates actin-myosin contraction via its receptor (S1P
2) in neighboring cells. The images above show epithelial sheets in normal and S1P2 mutant zebrafish larvae. In the mutant, the apoptotic cell (green) stays in the epithelial sheet and lacks the actin ring (red) seen in the wild-type tissue.

ResearchBlogging.orgGu, Y., Forostyan, T., Sabbadini, R., & Rosenblatt, J. (2011). Epithelial cell extrusion requires the sphingosine-1-phosphate receptor 2 pathway originally published in The Journal of Cell Biology, 193 (4), 667-676 DOI: 10.1083/jcb.201010075

May 23, 2011

“Hooolllly crap, this is so cool!” was what I said to my (accountant) husband after I read this paper. I did an interpretive dance to describe the many cool things in this particular paper, and I know you will too. Today’s image is from a recent paper about understanding the cellular mechanisms that underlie the very complicated mental disorder schizophrenia.

Schizophrenia is a mental disorder characterized by disorganized thought processes and emotional dysfunction. There is a strong genetic component to the disorder, yet the basic cellular mechanisms that occur in schizophrenic patients is not completely understood. Past studies have looked at post-mortem brains, which have taught biologists a lot about what a schizophrenic’s brain looks like. These studies, however, cannot help pinpoint the specific cells affected by schizophrenia and the molecular mechanisms that lead to the disorder. A recent paper does amazing acrobatics to figure out these unknowns. In this paper, Brennand and colleagues took fibroblasts from schizophrenia patients who have a high likelihood of having a genetic component to their disorder. These fibroblasts were reprogrammed into pluripotent stem cells, and then differentiated into neural progenitor cells and neurons. These neurons had decreased connectivity, diminished numbers of neurites, and altered levels of many key neuronal proteins and signals (glutamate receptors, for example…a biggie for neurons). Images above show the difference in neuronal connectivity in the neurons induced from stem cells in healthy (left) and schizophrenic (right) patients.

ResearchBlogging.orgBrennand, K., Simone, A., Jou, J., Gelboin-Burkhart, C., Tran, N., Sangar, S., Li, Y., Mu, Y., Chen, G., Yu, D., McCarthy, S., Sebat, J., & Gage, F. (2011). Modelling schizophrenia using human induced pluripotent stem cells Nature, 473 (7346), 221-225 DOI: 10.1038/nature09915

Adapted by permission from Macmillan Publishers Ltd, copyright 2011

May 19, 2011

If you read this blog, then you were probably the type of kid who used your toy microscope to look at the wound on your knee caused by your brother pushing you onto the ground (for example). You could see the skin around the scab stretching, and you knew there was some cool stuff going on there. I’m not sure if the authors from today’s image did this, but in a very sophisticated way they do now.

Our cells and tissues are equipped with the ability to repair wounds caused by normal wear-and-tear and injury. When the plasma membrane of a single cell is torn, the membrane and underlying cytoskeleton must be repaired. A recent paper describes the use of early fruit fly embryos to understand what occurs during single-cell wound repair. The early fly embryo is a fantastic model for understanding this event because of its ease of genetic manipulation and the large size of what is technically one cell. Abreu-Blanco and colleagues found that there are three phases in single-cell wound repair—brief expansion of the wound, contraction of the membrane, and clo
sure of the wound. Images above show the accumulation of actin around a healing wound. Left column shows the surface of wound, while the right column shows a cross section.

BONUS!! Check out a movie of the image above here. Still want more movies from this paper? Click here.

ResearchBlogging.orgAbreu-Blanco, M., Verboon, J., & Parkhurst, S. (2011). Cell wound repair in Drosophila occurs through three distinct phases of membrane and cytoskeletal remodeling originally published in The Journal of Cell Biology, 193 (3), 455-464 DOI: 10.1083/jcb.201011018

May 16, 2011

No cell is an island. Cells are influenced by their environment around them, and migrating cells are especially receptive to the surface they are crawling over. Today’s image is from an elegant study on how different forces regulate cell shape and movement.

Cell migration is a highly coordinated process that depends on many factors. One of these factors is the cell’s adhesion to the underlying substrate, and a recent paper clearly spells out how the adhesion strength of a substrate directly affects a migrating cell’s shape and motility. In the images above, migrating cells were placed on surfaces of different adhesion strength. Cells crawling with either low or high adhesion are slow and round compared to cells crawling on surfaces with medium adhesion strength. These alterations in adhesion affect the localization of actin (top, red) and the actin motor myosin (middle, green).

ResearchBlogging.orgBarnhart, E., Lee, K., Keren, K., Mogilner, A., & Theriot, J. (2011). An Adhesion-Dependent Switch between Mechanisms That Determine Motile Cell Shape PLoS Biology, 9 (5) DOI: 10.1371/journal.pbio.1001059

May 12, 2011

Some of my favorite proteins ride on the ends of microtubules. I don’t usually like to anthropomorphize proteins, but I always think of Dr. Strangelove hopping on the growing end of a microtubule (and I didn’t even like that movie!). Today’s image is from a paper that adds a satisfying piece to the mitotic spindle puzzle.

Astrin is a mitotic spindle protein that is required for proper alignment of chromosomes on the metaphase plate during mitosis. It wasn’t clear exactly what astrin is doing to promote chromosome alignment, or how astrin arrives at the right location. A recent paper paints a much more complete astrin story. Dunsch and colleagues found a novel protein called kinastrin that forms a complex with astrin and a few others. Astrin localizes to the plus ends of microtubules, and requires kinastrin to do so. The presence of this complex may be affecting microtubule dynamics directly, consistent with the chromosome alignment and spindle integrity problems seen in kinastrin- and astrin-depleted cells. Image above shows fluorescently-tagged astrin localized to the ends of microtubules. The different colors show the localization of astrin in subsequent time-lapse images (ie, the astrin moves with the end of the microtubule).

ResearchBlogging.orgDunsch, A., Linnane, E., Barr, F., & Gruneberg, U. (2011). The astrin-kinastrin/SKAP complex localizes to microtubule plus ends and facilitates chromosome alignment originally published in The Journal of Cell Biology, 192 (6), 959-968 DOI: 10.1083/jcb.201008023

May 9, 2011

“HELLO, my name is…tuft cell.” I’m sure a lot of folks wish that cells wore name tags to help identify them. In a sense, however, cells do wear name tags…we just have to figure out how to read them. A recent paper describes how to identify tuft cells in intestinal tissue, where they come from, and what jobs they perform.

Tuft cells are found in the intestinal epithelium, a tissue that is very dynamic and busy digesting food. Although tuft cells were identified in 1956, their origin, markers, and function remained unclear until recently. A group of researchers were recently able to identify markers that clearly define tuft cells within intestinal tissue. In addition, these biologists found that these cells come from a group of intestinal stem cells and function as secretory cells. In mice, tuft cells appear shortly after birth, as seen in the images above. Prior to birth (top), tuft cells are not found in the intestinal epithelium. However, after birth (middle, bottom), tuft cells can be detected by staining for DCLK1 (red, arrowheads), the tuft cell marker identified in the paper.

ResearchBlogging.orgGerbe, F., van Es, J., Makrini, L., Brulin, B., Mellitzer, G., Robine, S., Romagnolo, B., Shroyer, N., Bourgaux, J., Pignodel, C., Clevers, H., & Jay, P. (2011). Distinct ATOH1 and Neurog3 requirements define tuft cells as a new secretory cell type in the intestinal epithelium originally published in The Journal of Cell Biology, 192 (5), 767-780 DOI: 10.1083/jcb.201010127

May 5, 2011

So much depends on healthy cell division, so it is no wonder how magnificent the spindle checkpoint is. This checkpoint keeps our cells healthy and our biologists busy as they try to figure it all out.

The spindle checkpoint ensures that a dividing cell undergoes anaphase only when all chromosomes are properly attached the mitotic spindle. Without this checkpoint, cells may end up with an incorrect number of chromosomes. Recently, a group teased apart some of the specifics of the checkpoint by using a construct engineered in the lab. This construct fused the kinetochore protein Mis12 to the checkpoint protein Mad1, which blocks progression to anaphase when it localizes to kinetochores not attached to the spindle. This Mad1-Mis12 construct targeted Mad1 to kinetochores despite their orientation state on the mitotic spindle, meaning that this construct allowed researchers to distinguish between Mad1 checkpoint signaling and the initial orientation error signal. The images above show metaphase spindles in control cells (top) or cells with the Mad1-Mis12 construct (bottom). The construct (mCherry, red in merged image) localizes to kinetochores (CREST, blue in merged) attached to the spindle (tubulin, green).

ResearchBlogging.orgMaldonado, M., & Kapoor, T. (2011). Constitutive Mad1 targeting to kinetochores uncouples checkpoint signalling from chromosome biorientation Nature Cell Biology, 13 (4), 475-482 DOI: 10.1038/ncb2223
Adapted by permission from Macmillan Publishers Ltd, copyright 2011

May 2, 2011

The cytoskeleton is made of actin, microtubules, and intermediate filaments. Sometimes, those poor intermediate filaments fall out of the spotlight by the stage hogs, actin and microtubules. This is unfortunate, because intermediate filaments are quite beautiful, as you’ll see in today’s images.

Vimentin is an intermediate filament protein found in migrating cells. Migrating cells have lamellipodia, which are dynamic membrane ruffles found at the front of a migrating cell, and a recent paper looks at the role of vimentin in migration. Helfand and colleagues found that the disassembly of vimentin intermediate filaments at the cell’s periphery is important for the formation of lamellipodia and for motility. As seen in the images above, motile cells (top) do not have vimentin intermediate filaments in lamellipodia, and instead have a decreasing presence of long filaments as they approach the lamellipodia (a,b) and non-filamentous vimentin at the cell’s edge (c). Cells lacking lamellipodia (bottom), however, have vimentin intermediate filaments that extend to the cell’s periphery.

ResearchBlogging.orgHelfand, B., Mendez, M., Murthy, S., Shumaker, D., Grin, B., Mahammad, S., Aebi, U., Wedig, T., Wu, Y., Hahn, K., Inagaki, M., Herrmann, H., & Goldman, R. (2011). Vimentin Organization Modulates the Formation of Lamellipodia Molecular Biology of the Cell DOI: 10.1091/mbc.E10-08-0699