June 28, 2012

A week from today, my little girl turns 3 years old. As I’ve witnessed first-hand, kids grow up way too quickly. So, in that light, I’m already thinking through how I’ll give her “the talk.” We’ll start out easy, talking about birds and bees, then I’ll watch her squirm with discomfort while we talk about the real deal. Lucky for her, our sex talk will be peppered with phrases like zona pellucida and gamete recognition, thrown in for technical completeness. Today’s image is from a paper describing the proteins that allow sperm to attach to an egg.

Fertilization in mammals begins when sperm attaches to an egg’s zona pellucida, a glycoprotein membrane around the egg. Gamete recognition prevents fertilization between different species—human sperm cannot attach to a mouse egg, for example. In a recent paper, Baibakov and colleagues replaced mouse zona pellucida proteins with human zona pellucida proteins (ZP1-4). The transgenic mouse eggs containing human ZP2 protein allowed the attachment of human sperm. Human sperm were able to penetrate the zona pellucidae, but were not able to fertilize the mouse eggs. In the images above, human sperm are attached to a mouse egg with human ZP2 in the zona pellucida. Sperm heads are in blue, sperm tails are red.

ResearchBlogging.orgBaibakov B, Boggs NA, Yauger B, Baibakov G, & Dean J (2012). Human sperm bind to the N-terminal domain of ZP2 in humanized zonae pellucidae in transgenic mice. originally published in the Journal of Cell Biology, 197 (7), 897-905 PMID: 22734000

June 25, 2012

Sometimes the scary side of life sobers you up and wipes that stupid grin off your face. I just read that as of 2008, an estimated 1,178,350 people over the age of 13 were living with HIV in the United States. And, get this…20% were undiagnosed. So, let me stand up and clap loudly and throw flowers around the necks of the scientists trying to uncover all of HIV’s nasty secrets. Today’s image is from a paper describing how one of our own proteins binds to an HIV receptor, and negatively regulates HIV infection.

The HIV virus attaches to the membrane of a T-cell with the help of the HIV receptor proteins CD4 and CXCR4, which induce actin-mediated rearrangements that enhance entry of the virus into the cell. A recent paper identified a role for a protein called syntenin-1 in HIV entry. The adaptor protein syntenin-1 is implicated in many processes that involve polarization of the actin cytoskeleton, such as cell migration. According to Gordón-Alonso and colleagues, syntenin-1 is recruited to CD4 at the site of virus attachment to the cell, and negatively regulates virus entry by regulating actin reorganization. Overexpression of syntenin-1 inhibits HIV cell fusion and production, while depletion of syntenin-1 increases HIV entry. In the images above, T-cells were incubated with (bottom row) or without (top) HIV virus. In the presence of HIV virus, syntenin-1 (green) colocalizes with the cap of CD4 (red), which forms as a result of clustering of the receptor and enhances virus entry.

ResearchBlogging.orgGordón-Alonso M, Rocha-Perugini V, Alvarez S, Moreno-Gonzalo O, Ursa A, López-Martín S, Izquierdo-Useros N, Martínez-Picado J, Muñoz-Fernández MA, Yáñez-Mó M, & Sánchez-Madrid F (2012). The PDZ-adaptor protein syntenin-1 regulates HIV-1 entry. Molecular biology of the cell, 23 (12), 2253-2263 PMID: 22535526

June 21, 2012

There’s a song on the radio that you just love right now. You’re not sure what it is about the song that you love…the catchy chorus, the singer’s silky voice, the booming bass line, the touch of pan flute, whatever. If you’re musically-inclined, you start teasing the song apart in your head until you finally realize what it is (always, it’s the pan flute!). Knowing how to tease a complex problem apart is a key skill for any scientist, and today’s image is from a paper that pares down clathrin-coated pits to their bare minimum.

Clathrin coats are assembled cages of the scaffolding protein clathrin. These scaffolds deform a planar membrane into a curved membrane that is able to bud off during the uptake of material into the cell, a process called endocytosis. It was previously thought that clathrin-associated proteins helped to induce curvature in the membrane, but recently a group finds otherwise, in a study that describes the minimum requirements for clathrin-coated bud formation. In this paper, Dannhauser and Ungewickell monitored bud and vesicle formation using a cell-free system composed of brain lipids that artificially form vesicles called liposomes. They found that clathrin alone is sufficient to generate buds in a lipid membrane. In the images above, buds and vesicles were formed when liposomes were in the presence of clathrin, but lacking any other proteins able to induce membrane curvature. Many vesicles were, in fact, still attached to the liposomes via narrow membrane necks (arrows). 

ResearchBlogging.orgPhilip N. Dannhauser, & Ernst J. Ungewickell (2012). Reconstitution of clathrin-coated bud and vesicle formation with minimal components Nature Cell Biology, 14 (6), 634-639 : 10.1038/ncb2478
Adapted by permission from Macmillan Publishers Ltd, copyright ©2012

June 18, 2012

I love chromosomes. I am always in awe when I see these little things that are chock full of information and instructions for a cell, and in turn, a whole organism. When I think about how finely-tuned the dance is that allows chromosome segregation to happen correctly every time during mitosis, I am beyond impressed. Today’s image is from a paper describing how sister chromatids become bound to one another.

Sister chromatids remain held together until anaphase segregates them into two future daughter cells during mitosis. Chromatid cohesion is mediated by the cohesin complex of proteins and is established long before mitosis. A recent study identified the role of a protein called XEco2 in acetylating a cohesin complex member called Smc3, a step that is required for the establishment of chromatid cohesion. In addition, Higashi and colleagues found that this role of XEco2 is important prior to DNA replication, requiring the formation of the pre-replication complex. Later, DNA replication serves to stabilize cohesion between sister chromatids. In the images above, sister chromatids are bound together in control cells and in cells depleted of XEco1 (left two columns). In cell depleted of XEco2, XEco1 and XEco2 together, or cohesin (middle and right two columns), sister chromatids are not bound tightly to one another.

ResearchBlogging.orgHigashi TL, Ikeda M, Tanaka H, Nakagawa T, Bando M, Shirahige K, Kubota Y, Takisawa H, Masukata H, & Takahashi TS (2012). The Prereplication Complex Recruits XEco2 to Chromatin to Promote Cohesin Acetylation in Xenopus Egg Extracts. Current biology : CB, 22 (11), 977-88 PMID: 22560615
Copyright ©2012 Elsevier Ltd. All rights reserved.

June 14, 2012

You have this friend who is good at everything. He bakes cookies for sick kids at the hospital, he’s grand champion of all trivia nights at your local bar, he takes violin lessons every week, he works out every morning before the sun rises, and it’s just so annnnnooying how perfect he is and how much you want to be like him. Well, take that formins! You’re everywhere, and it’s annoying how good you are at your jobs! Today’s image is from a paper showing a novel role for the Diaphanous-related formin FMNL2.

Formins are actin filament-polymerizing proteins that are important in numerous cellular processes including cell polarity, cytokinesis, and cell migration. Although Diaphanous-related formins can form linear bundles of actin filaments similar to those in filopodia, the membrane protrusions seen on crawling cells, they haven’t been directly shown to play a role in filopodia formation. Block and colleagues recently found that the Diaphanous-related formin called FMNL2 accumulates at filopodia tips and lamellipodial membrane protrusions. In addition, FMNL2 drives actin elongation within filopidial tips and lamellipodia, in turn driving efficient cell migration, with the help of the well-studied polarity protein Cdc42. Images above show two time-lapse series of FMNL2 in crawling cells. FMNL2 is found at the filopodial tip (white arrows, left-hand images) and at the edge of a lamellipodial protrusion (arrowheads, right-hand images).

ResearchBlogging.orgBlock, J., Breitsprecher, D., Kühn, S., Winterhoff, M., Kage, F., Geffers, R., Duwe, P., Rohn, J., Baum, B., Brakebusch, C., Geyer, M., Stradal, T., Faix, J., & Rottner, K. (2012). FMNL2 Drives Actin-Based Protrusion and Migration Downstream of Cdc42 Current Biology, 22 (11), 1005-1012 DOI: 10.1016/j.cub.2012.03.064
Copyright ©2012 Elsevier Ltd. All rights reserved.

June 11, 2012

If you invited a protein to a party, it’d win your Twister tournament without a doubt. A protein is not just some static stick of cellular function, but can be a complicated structure that bends or twists in three dimensions and can interact with other domains (of itself or another protein). Today’s image is from a paper describing a thorough analysis of one domain on a Shroom protein.

Shroom (Shrm) proteins play important roles throughout development. Through their interaction with Rho kinase (Rock), Shroom proteins regulate the localization of the actin-myosin contractile network, which in turn affects cell and tissue shape. A recent paper describes a specific domain of Shrm, the SD2 domain, and its importance in the interaction between Shrm and Rock. In this paper, Mohan and colleagues present the structure of the SD2 domain and show the specific amino acid residues on the protein that are necessary for Shrm-Rock interaction, both in vertebrates and invertebrates. In the images above, mammalian cell cultures are treated with different Shrm SD2 constructs. Intact SD2 domains for both mouse (top) and fruit fly (middle) were able to constrict the cells expressing the construct (green cells). Without the SD2 domain (bottom), cells were unable to constrict.

ResearchBlogging.orgMohan, S., Rizaldy, R., Das, D., Bauer, R., Heroux, A., Trakselis, M., Hildebrand, J., & VanDemark, A. (2012). Structure of Shroom domain 2 reveals a three-segmented coiled-coil required for dimerization, Rock binding, and apical constriction Molecular Biology of the Cell, 23 (11), 2131-2142 DOI: 10.1091/mbc.E11-11-0937

June 7, 2012

 Al Green was most likely singing “Let’s Stay Together” to some babe he was in love with, but I’d like to imagine he was talking about cells. I’m not sure they play Al Green in the lab that today’s image comes from, but I’d suggest adding his work to their playlist (good advice for everyone, really). Today’s image is from a paper showing how cadherin’s structural changes affect cell adhesion.

Cadherins are transmembrane proteins that play an important role in cell-cell adhesion. Cell adhesion is a dynamic process that is highly regulated throughout development, during cancer progression, and for basic tissue function. A recent paper shows how physical and structural changes in certain cadherin domains affect the adhesive state of that cadherin. In this paper, Petrova and colleagues used a human colorectal tumor line of cells that don’t normally adhere to one another, but can be triggered to adhere and compact. By using a set of specialized monoclonal antibodies that can bind to certain states of active or inactive cadherin domains, Petrova and colleagues found that the structural changes in regions near calcium-binding sites, mediated by changes in another adhesion player called p120-catenin, affect adhesion activation. In the images above, cells treated with a control antibody (left) remain round and unattached, while cells treated with an adhesion-activating antibody (right) became attached and compact.

ResearchBlogging.orgPetrova, Y., Spano, M., & Gumbiner, B. (2012). Conformational epitopes at cadherin calcium-binding sites and p120-catenin phosphorylation regulate cell adhesion Molecular Biology of the Cell, 23 (11), 2092-2108 DOI: 10.1091/mbc.E11-12-1060

June 4, 2012

If you’re like me, you look forward to summer’s juicy blueberries. You’ll sprinkle or mix them into everything you eat, and sneak a big handful every time you open your fridge. You tell yourself that it’s all for the antioxidants. Just make a bigger rationalization leap and say you’re helping blueberries fight alongside dividing mitochondria to protect us from the evils of oxidative damage.

Mitochondria are the cell’s main source of energy, and without their dynamic dividing and fusing a cell can suffer. Neurological diseases such as Alzheimer’s, Parkinson’s, and Huntington’s are all associated with defects in mitochondrial division and fusion. A recent paper describes how mitochondrial division helps to protect neurons from oxidative damage, and in turn protects them from neurodegeneration. Kageyama and colleagues looked at postmitotic neurons in mice lacking Drp1, a protein that mediates mitochondrial division. In these neurons lacking Drp1, mitochondria extended into large tubules because of excess fusion, and showed an accumulation of oxidative damage and eventual neurodegeneration. This cell death could be reversed after application of antioxidants. The images above show Purkinje neurons in brain sections from 1, 3, and 6 month old mice (boxed areas show magnified images). Compared with control brain sections (top), Purkinje neurons lacking Drp1 (bottom) experienced dramatic neurodegeneration (90% of cells lost by 6 months).

ResearchBlogging.orgKageyama, Y., Zhang, Z., Roda, R., Fukaya, M., Wakabayashi, J., Wakabayashi, N., Kensler, T., Reddy, P., Iijima, M., & Sesaki, H. (2012). Mitochondrial division ensures the survival of postmitotic neurons by suppressing oxidative damage originally published in the Journal of Cell Biology, 197 (4), 535-551 DOI: 10.1083/jcb.201110034