October 28, 2010

If I could shrink down into a cell like in “Body Wars” at Disney’s Epcot, the first place I would travel to would be the kinetochore. The kinetochore is made of over 80 proteins which are each regulated to provide a mind-numbing level of complexity to its task of ensuring accurate chromosome segregation during mitosis.

Kinetochores are the structures on chromosomes where spindle microtubules attach during mitosis, and are responsible for generating the signal for accurate chromosome segregation. Because of the dynamic signaling required at the kinetochore, many proteins use phosphorylation to serve as rapid “molecular switches.” Phosphorylation is the addition of a phosphate group onto a protein, which alters the protein’s activity in some way, while dephosphorylation reverses the switch. Aurora B is a protein that phosphorylates many kinetochore proteins during mitosis, and a recent paper looks at how Aurora B is regulated by a protein called Sds22, which modulates a protein responsible for dephosphorylation. Images above show mitotic spindles (green) in control (top) and Sds22-depleted (bottom) human cells. Hec1 is a kinetochore protein (right, red in merged) that is phosphorylated by Aurora B; the phosphorylated form of Hec1 is the center image (blue in merged). Surprisingly, Sds22 depletion caused a decrease in phosphorylation of Hec1, suggesting that Sds22 modulates the phosphorylation activity of Aurora B.

Reference: Markus Posch, Guennadi A. Khoudoli, Sam Swift, Emma M. King, Jennifer G. DeLuca, and Jason R. Swedlow, 2010. Originally published in Journal of Cell Bioloy. doi: 10.1083/jcb.200912046. Paper can be found here.

BONUS!! Want to play with the authors' data yourself? Click here.

October 25, 2010

Sperm are very powerful little workers—not only do they fertilize eggs in order to bring new life into this world, but they have to go on an amazing journey to do so. Thankfully, they are usually made correctly and have millions of fellow sperm brothers to make sure that fertilization happens.

Both the X and Y chromosomes have multiple copies of genes that are important for sperm differentiation. One of these genes is called Sly, which is on the Y chromosome and regulates sex chromosome expression and sperm differentiation. A recent paper looks at two Sly-related genes on the X chromosome, called Slx and Slx-like1, and finds that they are important for proper sperm differentiation, and thus male fertility. Images show the head-tail connections in sperm from normal (top left, middle) and Slx/Slx-like1-deficient mice. The reduced motility of sperm in Slx/Slx-like1-deficient mice is like due to these abnormal head-tail connections, including partially detached tails (top right), incorrect alignment of the head and tail (bottom left), or abnormally-shaped tails (bottom middle, right).

Reference: Julie Cocquet, Peter J. I. Ellis, Yasuhiro Yamauchi, Jonathan M. Riel, Thomas P. S. Karacs, Áine Rattigan, Obah A. Ojarikre, Nabeel A. Affara, Monika A. Ward, and Paul S. Burgoyne. Authors’ Molecular Biology of the Cell paper can be found here.

October 21, 2010

The development of a single eye is a complicated process. Multiply that by 750, the number of eyes in the fruit fly’s compound eye, and you’re bound to be impressed by the amazing cellular and developmental events that have to occur in order for a fruit fly to find its way to lunch.

During development of the Drosophila eye, photoreceptor neurons secrete an epidermal growth factor receptor called Spi. Spi can be secreted from either the cell body or axonal terminus of the neuron, and this polarized secretion leads to different responses from the same signal. A recent paper highlights the role of an ER-localized protein called Rho-3 in determining the site of Spi secretion in the axonal terminus. Images above show the developing eye disc and lamina of flies with (top) or without (bottom) Rho-3. Without Rho-3, the lamina (dotted lines) does not express Elav (red), which is normally expressed when Spi is secreted from photoreceptors. Black and white images show Elav staining alone.

Reference: Shaul Yogev, Eyal D. Schejter, Ben-Zion Shilo. Authors’ PLoS Biology paper can be found here.

October 18, 2010

Whenever I see a paper with the word “sarcomere” in the title, I can be sure to see lovely images of these ordered structures found in muscle cells. In my type-A personality’s quest for order, these images are always soothing.

A sarcomere is the basic unit of a muscle and gives muscle its striated appearance. Sarcomeres contain overlapping actin and myosin motors that function in the contraction of each unit; multiply each sarcomere’s contraction many many times, and you’re able to lift your coffee mug. It was believed for a while that mature sarcomeres were very rigid structures, but recently that view has shifted. A recent paper describes the function of a sarcomere protein called Lmod in actin nucleation, suggesting its role in dynamic repair and remodeling of mature sarcomeres. Image above shows a chicken cardiac muscle cell with Lmod in green and Z-lines, which are the sarcomere's outside anchor points for actin, in red (α-actinin). Zoomed images of the boxed region show Lmod on either side of the center of the sarcomere, called the M-line, suggesting it is found at the ends of actin filaments.

Reference: Aneta Skwarek-Maruszewska, Malgorzata Boczkowska, Allison L. Zajac, Elena Kremneva, Tatyana Svitkina, Roberto Dominguez, and Pekka Lappalainen. Authors’ Molecular Biology of the Cell paper can be found here.

October 14, 2010

After going through so many papers for this blog, I’ve realized how ridiculously cool some pathogens are in how they infect and spread in host cells. The parasite featured in the above images takes the proverbial cake...an infected, proliferating cake.

The parasite Theileria spreads its infection to new host cells differently from many other pathogens, which replicate within and exit from the cell to invade other cells. A recent paper shows how this parasite stays in the cell and divides along with the cell during mitosis, co-opting the cell’s own mitotic spindle in order to end up in both daughter cells. Theileria also manipulates the cell’s own signaling in order to allow continuous growth and to prevent apoptosis (programmed cell death), expanding the infection. Images above are of infected cells at different mitotic stages, with microtubules (left; red in merged images), a Theileria marker (middle left; green in merged images), and DNA (blue in merged images). During metaphase (top), anaphase (middle), and telophase/cytokinesis (bottom), Theileria attaches itself to the microtubules of the mitotic spindle.

Reference: Conrad von Schubert, Gongda Xue, Jacqueline Schmuckli-Maurer, Kerry L. Woods, Erich A. Nigg, Dirk A. E. Dobbelaere. Authors’ PLoS Biology paper can be found here.

October 11, 2010

Starting in our high school biology classes, we all learned that mitochondria are the “powerhouses” of the cell. However, how many of us knew mitochondria could play a role in diverse processes ranging from hormone secretion to cell differentiation?

Calcium is a major regulator and signal in countless cellular processes. Mitochondria participate by taking in and storing calcium, which helps buffer the amount of free calcium in the cell. A group recently became the first to identify one of the proteins important for mitochondrial calcium uptake. Images above show this protein, called MICU1 (green), localizing onto mitochondria (red); the merged image (right) shows yellow where the two signals are colocalized.

Reference: Fabiana Perocchi, Vishal M. Gohil, Hany S. Girgis, X. Robert Bao, Janet E. McCombs, Amy E. Palmer, and Vamsi K. Mootha. Adapted by permission from Macmillan Publishers Ltd: Nature 467: 291-296, copyright 2010. Paper can be found here.

October 7, 2010

There are a few processes in a cell that simply blow my mind as I try to grasp how such a complex task is accomplished correctly every time. Cytokinesis is one of them, and is an absolutely elegant process to watch.

Cytokinesis is the step during cell division that physically splits a cell in half. Cytokinesis depends on actin, myosin, and many regulatory proteins, and a recent paper helps sort out where and how these proteins interact. Image above shows two cells undergoing cytokinesis, with microtubules remaining from the mitotic spindle (red), chromosomes (blue), and an actin-nucleating factor called mDia2 (green). The control cell (top) shows mDia2 localization at the cleavage furrow, the indentation of membrane at the beginning of cytokinesis; however, without a protein that regulates an mDia2 activator, mDia2 levels are reduced at the cleavage furrow.

Reference: Sadanori Watanabe, Katsuya Okawa, Takashi Miki, Satoko Sakamoto, Tomoko Morinaga, Kohei Segawa, Takatoshi Arakawa, Makoto Kinoshita, Toshimasa Ishizaki, and Shuh Narumiya. Authors’ Molecular Biology of the Cell paper can be found here.

The Node

Hey everyone! Head on over to The Node today to check out a lovely image of Drosophila germline cysts. The Node invited me to contribute to their forum, and of course I jumped at the opportunity to be part of their community. The site is a forum for developmental biologists, hosted by the journal Development, so I'll be mostly featuring developmental biology images over there.

October 4, 2010

Today’s image is a first for HighMag…I’m showing a second image from the paper that provided Thursday’s image. This is a fantastic paper, and has great images using different techniques to show the authors’ take-home message.

M2 is a protein from the influenza virus that is able to shape and release a newly-replicated budded virus particle out of an infected cell, allowing the infection of more cells. Thursday’s image showed the ability of a domain of the M2 protein to induce budding on a synthesized vesicle. Today’s image shows the localization of M2 at the neck of budding virus particles (red arrows). The authors determined the localization of M2 using electron microscopy and immuno-gold labeling, which means that tiny gold beads are attached to antibodies able to find M2. The little beads represent M2 localization in the image above, with bottom images showing a higher magnification.

Reference: Jeremy S. Rossman, Xianghong Jing, George P. Leser and Robert A. Lamb. Cell 142 (17), 902-913. ©2010 Elsevier Ltd. All rights reserved. Paper can be found here.