Satyajit Mayor

Director

National Centre for Biological Sciences

Tata Institute for Fundamental Research

Bangalore, India

“Building membrane domains at the surface of living cells triggered by signaling receptors”

How cells build specific membrane domains has been a subject of much debate and controversy. Our work studying the organization of outer leaflet tethered GPI-anchored proteins (GPI-APs) provides an attractive mechanism for the regulated formation of specific membrane domains. Nano-clusters of GPI-APs driven by the dynamics of contractile actin machinery operating at the inner leaflet create a membrane region of distinct composition. While an understanding of the physical principles behind the active mechanics of actin filaments and myosin and its ability to form contractile actin asters is emerging, the molecular machinery behind the generation of dynamic actin and its coupling to inner leaflet lipids is lacking. Contractile filaments of actin detected by their ability to cluster outer leaflet GPI-APs and transmembrane proteins with actin-filament binding domains (TM-AFBDs) are nucleated locally via ligand-dependent receptor signaling. This is exemplified by the activation of integrin-signaling wherein both soluble and surface-tethered RGD-containing ligands activate Focal Adhesion Kinase (FAK) and src-mediated kinases. This stimulates RhoGTPases, triggering actin-filament production via specific formins. In parallel, Rho-mediated ROCK activation regulates myosin activity, resulting in the nanoclustering of GPI-APs and TM-AFBDs.  This completes the machinery required for coupling dynamic actin activity at the inner leaflet with outer leaflet GPI-APs. The resultant nanoclustering of GPI-APs is necessary for mediating integrin receptor function, in the context of integrin-triggered cell spreading. This machinery is likely to provide a very general way of generating domains with specific composition in the vicinity of signaling receptors. 

Satyajit "Jitu" Mayor studied Chemistry at IIT, Mumbai, and obtained his Ph.D. in Life Sciences from The Rockefeller University, New York. He was a post-doctoral fellow at Columbia University, New York, where he developed tools to study the trafficking of membrane lipids and GPI-anchored proteins in mammalian cells using quantitative fluorescence microscopy. Currently he is Senior Professor and Director at National Centre for Biological Sciences Tata Institute for Fundamental Research, and the Institute for Stem Cell Biology and Regenerative Medicine in Bangalore, India. He is a Fellow of the Indian Academy of Sciences, and National Academy of Sciences, and a foreign associate of the US National Academy of Sciences and EMBO.  He is a recipient of a number of national and international awards including the Shanti Swarup Bhatnagar Award, The World Academy Prize (TWAS) for Biology, and the Infosys Prize for Life Sciences.

PI4D Seminar

Friday, July 7, 2017

11:15 – 12:15 PM in

MJIS 1001