Giulia Baldini, M.D. Ph.D.
Role of SNAREs and Rab proteins in secretion by endocrine cells and insulin sensitive cells
Constitutive exocytosis is a process by which newly synthesized proteins and lipids are transported from the ER to the cell surface by vesicular traffic. At the cell surface, proteins and lipids become constituents of the plasma membrane or are secreted in the extracellular space. Specialized cells, such as endocrine cells, neurons, acinar cells of the pancreas, mast cells, insulin-sensitive cells and many other cell types have, in addition to the constitutive secretory pathway, one or more regulated secretory pathways. These cells store vesicles like dense core granules and synaptic vesicles. Regulated secretory vesicles are released only in response to a stimulus. Neurotransmission in neurons, release of hormones by endocrine cells, release of histamine by mast-cells and exocytosis of glucose transporter-containing vesicles in fat cells are examples of different types of regulated secretory events. The work in my lab has focused on the molecular mechanisms of regulated exocytosis in endocrine cells and insulin-sensitive cells. Release of hormone-containing granules is a process mediated by SNAP-25, syntaxin, VAMP, Rab3 and synaptotagmin families of proteins. We are studying their mechanism of action by using a combination of biochemical and cell biological techniques.
Recent References:G. Wang, J. W. Witkin, G. Hao, V. A. Bankaitis, P. E. Scherer, and G. Baldini (1997) Syndet is a novel SNAP-25 related protein localized at the plasma membrane. J. Biol Sci . 110, 505-513.
G. Baldini , G. Wang, M. Weber, R. Bareggi, M. Zweier, J. W. Witkin and A. Martelli. (1998) Expression of Rab3D N135I inhibits regulated secretion of ACTH in AtT-20 cells. J. Cell Biol. 140, 305-313.
S. Rea, S. Mc Intosch, L. Macaulay, L. Matin, T. Ramsdale, G. Baldini , D. E. James. (1998) Syndet: an adipocyte t-SNARE involved in the insulin-induced translocation of Glut4 to the cell surface. J. Biol Chem. 273, 18784-18792.
M. Iezzi, P. Meda, A. Charollais, G. Baldini, F. Darchen, C. B. Wollheim, and R. Regazzi. (1999) Subcellular distribution and functional role of Rab3A, B, C and D isoforms in insulin-secreting cells. Molecular Endocrinology , 13, 202-212.
D. K. Koticha, S. J. Huddleston, J. W. Witkin and G. Baldini . (1999) Role of the cysteine-rich domain of the t-SNARE component, syndet, in membrane binding and subcellular localization. J. Biol Chem , 274, 9053-9060.
A. M. Martelli, G.Tabellini, D. K. Koticha, R. Bareggi, and G. Baldini <2000> Rab3A and Rab3D control the total granule number and the fraction of granules docked at the plasma membrane in PC12 cells. Traffic , 1, 976-986