September 30, 2010

I love proteins that bend membranes. Bending a membrane is an amazing feat…if we could relate the work of one of these proteins to a large scale human example, I’m sure we’d all be impressed. Today’s post is about one of these proteins, and it comes from a virus.

A recent paper looks at the mechanism that influenza virus uses when a newly replicated virus particle buds out of the cell’s plasma membrane, in order to infect other cells. While many viruses use proteins hijacked from the infected cell for this budding process, influenza virus uses its own protein called M2. M2 alters the curvature of the plasma membrane in order to shape the bud, and mediates membrane scission which is required for release of the virus particle. Images are of synthesized vesicles without (left) or with (right) the domain of M2 thought to bend membrane, and shows that this domain alone is able to induce budding.

Bonus!! Video of entire M2 protein inducing budding in a synthesized vesicle can be found here.

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.

September 27, 2010

One might think that the higher the magnification we use to see inside a cell, the more we can know. However, some of the best discoveries come when we take a step back and see how cells move. The image today is a great example of this.

Cell migration is a complex process requiring rapid changes in the regulation and mechanics of the cytoskeleton. Dictyostelium is an amoeba that migrates using similar mechanisms to mammalian cells, so is frequently used as a model for understanding chemotactic migration…a recent paper does just this. Image above shows chemotaxis of Dictyostelium cells towards a signal placed in a pipette tip. The normal cells (left) move towards the tip after 20 minutes, as seen by their elongated shape and membrane protrusions reaching towards the tip. Without a protein called NHE1 that helps regulate pH (middle), the cells no longer migrate towards the pipette tip and have a globular shape. However, once an actin-interacting protein called Aip1 was introduced to cells lacking NHE1 (right), they were able to restore chemotaxis towards the pipette tip.

Reference: Chang-Hoon Choi, Hitesh Patel, and Diane L. Barber. Authors’ Molecular Biology of the Cell paper can be found here.

September 23, 2010

Retinal detachment occurs when the retinal pigment epithelium (RPE) loses its adhesion to the underlying photoreceptors, and is a sight-threatening condition. A recent paper has looked at the role of a protein called CLIC4 in this adhesion, and found decreased retinal adhesion in CLIC4-suppressed RPE cells. Images are of normal (top) and CLIC4-suppressed (bottom) retinal sections, showing the disorganization of the photoreceptors in the outer nuclear layer (ONL) of retinas with CLIC4-suppressed RPE cells.

Reference: Jen-Zen Chuang, Szu-Yi Chou, and Ching-Hwa Sung. Authors’ Molecular Biology of the Cell paper can be found here.

September 20, 2010

Cilia are beating hair-like projections protruding from the surface of some cells, and can function in propelling single-cell organisms or moving fluid over fields of cells with many cilia. The structure of cilia is precise and remarkable due to the arrangement of microtubules, the microtubule motor dynein, and associated proteins. Mutations in a protein called CEP290 cause cilia-related diseases in humans, and a recent paper uses the flagella, structures similar to cilia, of the single cell algae Chlamydomonas reinhardtii to understand the role of CEP290 in ciliary function. Image above shows a cross-section of the transition zone at the base of the flagella in normal or cep290 mutant cells. While the normal cells had Y-shaped connectors joining the microtubules to the flagellar membrane (arrowheads), the mutant cells did not.

Reference: Branch Craige, Che-Chia Tsao, Dennis R. Diener, Yuqing Hou, Karl-Ferdinand Lechtreck, Joel L. Rosenbaum, and George B. Witman, 2010. Originally published in Journal of Cell Bioloy. doi: 10.1083/jcb.201006105. Paper can be found here.

September 16, 2010

The endoplasmic reticulum (ER) is a very large organelle made up of continuous membrane tubules and sheets, where membrane-bound and secreted proteins are made and sorted. The ER is very dynamic, with membrane constantly rearranging, and does so with the help of microtubules. A recent paper looks at ER dynamics and through the use of live imaging shows ER sliding along a population of microtubules that are stabilized by acetylation modifications. Image above shows typical ER dynamics—the ER at the first time point is in green, and the ER at 30 seconds later is in red. The yellow arrow shows a region where the ER did not move, while the white arrow shows a sliding event.Reference: Jonathan R. Friedman, Brant M. Webster, David N. Mastronarde, Kristen J. Verhey, and Gia K. Voeltz, 2010. Originally published in Journal of Cell Bioloy. doi: 10.1083/jcb.200911024. Paper can be found here.

BONUS! Cool movie of above image can be found here.

September 13, 2010

A telomere is the end region of a chromosome that helps protect it from shortening during DNA replication, and has a repetitive and characteristic DNA sequence. A recent paper looks at the role of a protein called Rap1 in both telomere function and transcriptional regulation. Rap1 is important to prevent telomere recombination (exchange of segments of DNA) and fragility, which can lead to events characteristic of cancer in mammals. Images above show chromosomes from mouse cells without Rap1. The telomere signal on each chromosome strand is labeled with one color, and telomere recombination can be seen when the signals are exchanged (arrows).

Reference: Paula Martinez, Maria Thanasoula, Ana R. Carlos, Gonzalo Gómez-López, Agueda M. Tejera, Stefan Schoeftner, Orlando Dominguez, David G. Pisano, Madalena Tarsounas and Maria A. Blasco. Reprinted by permission from Macmillan Publishers Ltd: Nature Cell Biology 12, 768–780, copyright 2010. Paper can be found here.

September 9, 2010

The protein spectrin is found at the cell’s plasma membrane and serves to provide shape and stability to a cell. In addition to serving as part of a cell’s scaffolding network, spectrin has also been assigned functions in cell polarity and membrane traffic. A recent paper has looked at the requirement for spectrin, and its adaptor protein ankyrin, in neurons and other cells in the fruit fly Drosophila. Image above shows two salivary glands with normal (left) or increased (right) levels of spectrin. Too much spectrin in this tissue leads to changes in cell shape and polarity.

Reference: G. Harper Mazock, Amlan Das, Christine Base, and Ronald R. Dubreuil. Authors’ Molecular Biology of the Cell paper can be found here.

September 6, 2010

Strong cell-cell adhesion is crucial for tissue organization during development. A complex of three proteins—cadherin, α-catenin, and β-catenin—play an important role in adhesion by organizing and regulating the actin cytoskeleton. A recent paper demonstrates how α-catenin functions within this complex and with actin in the developing worm embryo, and shows that this complex is regulated differently from the mechanism in mammals. Image is a C. elegans embryo with a mutant form of α-catenin (blue and green) and actin (yellow and magenta). Both are localized at cell junctions in normal embryos, but in this mutant there is reduced α-catenin and gaps of actin localization at cell-cell junctions.

Reference: Image is by Stephanie L. Maiden, and is the cover image cover for the August issue of PNAS, which can be found here. Accompanying paper is by Adam V. Kwiatkowski, Stephanie L. Maiden, Sabine Pokutta, Hee-Jung Choi, Jacqueline M. Benjamin, Allison M. Lynch, W. James Nelson, William I. Weis, and Jeff Hardin, and can be found here.

September 2, 2010

The planar cell polarity (PCP) pathway functions to orient cells within the plane of an epithelial tissue. The fruit fly is a great model system for studying the PCP pathway—the bristles on the fly’s back and wing hairs grow in a certain direction as a result of the orientation of the cells, making it easy for researchers to see problems in the pathway. A recent paper has found a role for a transmembrane proton pump protein called VhaPRR in PCP signaling. Images are election micrographs of bristles with (left) or without (right) normal levels of VhaPRR. Without VhaRRR, the bristles are disoriented, as well as the small epithelial hairs underneath.

Reference: Tobias Hermle, Deniz Saltukoglu, Julian Grünewald, Gerd Walz and Matias Simons. Current Biology 20(14): 253-258. ©2010 Elsevier Ltd. All rights reserved. Paper can be found here.