Phosphoinositides in Regulated Exocytosis. Secretion of neurotransmitters and hormones involves multiple membrane trafficking events, including secretory granule biogenesis at the Golgi, active transport to the cell periphery, docking and fusion at the plasma membrane, and retrieval following exocytosis. Each of these steps is controlled in part by phosphoinositide lipids. We are studying how the biosynthesis of these phosphoinositides is regulated during stimulus-secretion coupling in neuroendocrine and insulin-releasing cells. Specifically, we wish to understand the function and regulation of phosphoinositide kinases and phosphatases in the various membranes of the secretory pathway.
Role of Dynamin in Membrane Vesicultion. Dynamin is a large (100 kDa) GTPase that induces membrane budding by polymerizing around the necks of nascent vesicles. The GTPase activity of dynamin is crucial for synaptic and secretory vesicle biogenesis and recycling, as well as for clathrin-dependent receptor-mediated endocytosis. We use a variety of biophysical techniques, including rapid-reaction kinetics, analytical ultracentrifugation, and fluorescence correlation spectroscopy to characterize dynamin interactions in vitro and in live cells. Our goals are to understand how dynamin and its binding partners generate force for membrane bending during vesicle formation, and how phosphoinositide lipids regulate the dynamin GTPase reaction.
Guanylyl cyclase B in cell motility and differentiation. Guanlyl cyclase B (GCB) is the receptor for C-type natriuretic peptide (CNP). We have evidence from GCB-null mice that CNP regulates differentiation of chondrocytes and adipocytes. Chondrocytes and preadipocytes from these mice fail to mature, resulting in dwarfism and in reduction of adipose tissue. We are attempting to understand how CNP controls transcription factors involved in the differentiation of these cell types.
RESEARCH INTERESTS
Phosphoinositides in Regulated Exocytosis.
Role of Dynamin in Membrane Vesiculation.
Guanylyl cyclase B in cell motility and differentiation.
RECENT PUBLICATIONS
Bagatolli, L.A., Binns, D.D., Jameson, D.M., and Albanesi, J.P., "Activation of dynamin II by POPC in giant unilamellar vesicles: A two-photon fluorescence microscopy study." J. Protein Chem., 21:383-391, 2002
Markin, V.S. and Albanesi, J.P., "Membrane fusion: Stalk model revisited." Biophys. J., 82:693-712, 2002
Yaradanakul A., Feng S., Shen C., Lariccia V., Lin MJ., Yang J., Kang T M., Dong P., Yin HL., Albanesi JP., Hilgemann DW., "Dual control of cardiac Na+ Ca2+ exchange by PIP2: electrophysiological analysis of direct and indirect mechanisms." J Physiol, 582 (Pt 3):991-1010, August 2007
Rodgers MJ., Albanesi JP., Phillips MA., "Phosphatidylinositol 4-kinase III-beta is required for golgi maintenance and cytokinesis in Trypanosoma brucei." Eukaryot Cell, 6(7):1108-18, July 2007
Barylko B., Wlodarski P., Binns DD., Gerber SH., Earnest S., Sudhof TC., Grichine N., Albanesi JP., "Analysis of the catalytic domain of phosphatidylinositol 4-kinase type II." J Biol Chem, 277(46):44366-75, November 2002
SIGNIFICANT PUBLICATIONS
Wang YJ, Wang J, Sun HQ, Martinez M, Sun YX, Macia E, Kirchhausen T, Albanesi JP, Roth MG, Yin HL., "Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi." Cell, 114(3):299-310, August 2003
Wei YJ., Sun HQ., Yamamoto M., Wlodarski P., Kunii K., Martinez M., Barylko B., Albanesi JP., Yin HL., "Type II phosphatidylinositol 4-kinase beta is a cytosolic and peripheral membrane protein that is recruited to the plasma membrane and activated by Rac-GTP." J Biol Chem, 277(48):46586-93, November 2002
Barylko B, Gerber SH, Binns DD, Grichine N, Khvotchev M, Sudhof TC, Albanesi JP., "A novel family of phosphatidylinositol 4-kinases conserved from yeast to humans." J Biol Chem, 276(11):7705-7708, March 2001
Achiriloaie, M., Barylko, B., and Albanesi, J.P., "Essential role of the dynamin pleckstrin homology domain in receptor-mediated endocytosis." Mol. Cell Biol., 19:1410-1415, February 1999
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