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Cellular Organisation and Signalling

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Only Connect: how cells tune-in via multiple mechanisms of endocytosis

No cell is an island: every second multitudes of atoms and molecules enter and exit. Thus does the cell breathe and converse, constantly sampling and responding to its environment. The rich flux of nutrients, signalling chemicals and ions indicates that the cell boundary is no sleepy frontier but a dynamic, highly-enabled transport facilitator. In fact, even just for ions and small molecules, inbound, the surrounding (plasma) membrane provides three possibilities: channels, carrier proteins and diffusion. For large molecules, which are ushered in via pinched-off in-pocketings of the plasma membrane, the known variations of this process (endocytosis) are even more numerous, and further discoveries are certain. Our laboratory is committed to exploring all facets of intake by endocytosis, exploiting new fluorescence microscopy techniques to directly visualize the in vivo nano-structure and activity of endocytic components. Our starting point is understanding the physico-chemical nature of the plasma membrane itself, and with Prof. Madan Rao we are pursuing our finding that the patches (or rafts) that concentrate molecules such as lipids and proteins in the membrane are much smaller than previously thought. Next, we are fleshing out the molecular basis of a novel mode of endocytosis in which these rafts are used but in which, uniquely to date, membrane in-pocketings are pinched off as vesicles without recourse to the girdling protein dynamin. The crucial significance of endocytic intake, cellular eavesdropping, for the whole organism is also being examined, in the model genetic system, Drosophila, with Prof. KS Krishnan and in the human immune system, with Dr S Rath.

Selected Publications :

  • Gowrishankar K, Ghosh S, Saha S, C R, Mayor S, Rao M. (2012) Active remodeling of cortical actin regulates spatiotemporal organization of cell surface molecules. Cell, 149(6):1353-67. 
  • Kumari S, Mayor S. (2008) ARF1 is directly involved in dynamin-independent endocytosis, Nat Cell Biol, 10(1):30-41.

  • Sabharanjak, S., Sharma, P., Parton, R.G. and Mayor, S. (2002). GPI-anchored proteins are delivered to recycling endosomes via a distinct cdc42-regulated, clathrin-independent pinocytic pathway, Developmental Cell , 2, 411-23.

  • Varma, R., and Mayor, S. (1998). GPI-anchored proteins are organized in submicron domains at the cell surface. Nature, 394, 798-801.