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Regulation of membrane vesicle trafficking and phototransduction by lipid-modifying signaling enzymes
Professor, Pharmacological Sciences
Center for Molecular Medicine, room 438
M.D., Ph.D., University of Pennsylvania
Postdoctoral, University of California, San Francisco
Selected Publications
Lab Page
Our lab is interested in roles undertaken by a superfamily of signal transducing enzymes involved in development, phototransduction, regulated exocytosis, and changes in cell morphology.
We are presently characterizing several new genes that control different aspects of these processes. Experiments in progress include misexpressing the genes using transgenic technology and inactivating them to attempt to determine their function using homologous recombination or RNA interference. In addition, we are exploring the structure, control of subcellular localization, and cell biological function of the proteins encoded by them. Experimental techniques and systems include molecular biology, biochemistry, mammalian cell culture, yeast, Drosophila, and mice. Relevant physiological systems include diabetes (translocation of glucose transporters in fat and muscle cells in response to insulin) and regulated exocytosis of hormones by neuroendocrine cells.
Zhang, Y, Altshuller, Y.A., Morris, A.J., and Frohman, M.A. (1999) Loss of Receptor Regulation by a Phospholipase D1 mutant unresponsive to Protein Kinase C. EMBO J., 18:6339-6348.
Honda, A., Nogami, M., Yokozeki, T., Yamazaki, M., Nakamura, H., Watanabe, H., Kawamoto, K., Nakayama, K., Morris, A.J., Frohman, M.A., and Kanaho, Y. (1999) Phosphatidylinositol 4-phosphate 5-kinasea is a Downstream Effector of the Small G Protein ARF6 in Membrane Ruffle Formation. Cell, 99:521-532.
Zhang, Y., Redina, O., Altshuller, Y.M., Yamazaki, M., Ramos, J., Chneiweis, H., Kanaho, Y., and Frohman, M.A. (2000) Regulation of PLD1 and PLD2 expression levels by Pea-15, a novel PLD-interacting protein. J. Biol. Chem., 275: 35224-35232
Du, G., Altshuller, Y.M., Kim., Y., Han, J.M., Ryu, S.H., Morris, A.J., and Frohman, M.A. (2000) Dual requirement for Rho and protein kinase C in direct activation of phospholipase D1 through G-protein coupled receptor signaling. Mol. Biol.Cell, 11:4359-4368.
Vitale, N., Caumont-Primus, A.-S., Chasserot-Golaz, S., Du, G., Wu, S., Sciorra, V.A., Morris, A.J., Frohman, M.A. and Bader, M.-F. (2001) Phospholipase D1 : a key factor for the exocytotic machinery in neuroendocrine cells. EMBO J., 20:2424-34.
Humeau, Y., Vitale, N., Chasserot-Golaz, S., Dupont, J.-L., Du, G., Frohman, M.A., Bader, M.-F. and Poulain, P. (2001) A role for phospholipase D1 in neurotransmitter release. P.N.A.S. 98:15300-5.
Du, G., Morris, A.J., Sciorra, V.A., and Frohman, M.A. (2002) G-protein coupled receptor regulation of Phospholipase D. In : G-protein Pathways. Methods in Enzymology (Hildebrandt, J.D. and Iyengar, R., Editor). 345:265-274.
Vitale, N., Chasserot-Golaz, S., Bailly, Y., Morinaga, N., Frohman, and Bader, M.-F. (2002) Calcium-regulated exocytosis of dense core vesicles requires the activation of ARF6 by ARNO at the plasma membrane. J. Cell Biol.159:79-89.
Huang, P. and Frohman, M.A. (2003) Phospholipase D and Glut-4 trafficking. Diabetes Metabolism Research and Reviews. In press
Du, G., Altshuller, Y.M., Vitale, N., Huang, P., Chasserot-Golaz, S.,Morris, A.J., Bader, M.F., and Frohman, M.A. (2003) Regulation of Phospholipase D subcellular cycling through coordination of multiple membrane association motifs. J. Cell Biol. in press.
Janssens, H., LaLonde, M., Yun, S., Crosby, J., Redina, O., Du, G., Olive, V., Altschuller, Y.M., Gergen, J.P., and Frohman, M.A. Phospholipase D is required for the progression of cellularization in Drosophila and functions by regulating vesicle trafficking. Submitted
