University of Toronto Biochemistry

	Sergio Grinstein Professor Ph.D. Mexico, 1976
	Hospital for Sick Children, McMaster Building, Room 5006 416-813-5727 sga@sickkids.ca

Biological Membranes and Ion Transport

Research Synopsis

Two major areas are under study in my laboratory. The first one investigates the molecular mechanisms utilized by white blood cells to eliminate infectious organisms. More specifically, we are studying the processes whereby macrophages and neutrophils migrate to sites of infection, ingest microbes and destroy them.

The second area deals with the regulation of ion transport and pH of intracellular compartments. We have devised means of measuring the pH and ionic composition of individual organelles within intact live cells and are currently investigating the identity and properties of the molecules responsible for ionic regulation.

Future Research
We anticipate to make extensive use of molecular biology and single-cell spectroscopy to pursue our studies of innate immunity and of ion transport and pH regulation.

Selected Publications

Yeung, T., Ozdamar, B., Paroutis, P. and Grinstein, S. (2006) Lipid metabolism and dynamics during phagocytosis.Curr. Op. Cell Biol. 4 :429-437.

Suh, C.I., Stull, N.D., Li, X.J., Tian, W., Price, M.O., Grinstein, S., Yaffe, M.B., Atkinson, S. and Dinauer, M.C. (2006) The phosphoinositide-binding protein p40 phox activated the NADPH oxidase during Fc g IIA receptor-induced phagocytosis. J. Exp. Med. 203 :1915-1925.

Mero, P., Huang, Z.Y., Kim, M.-K., Schreiber, A.D., Grinstein, S. and Booth, J.W. (2006) Phosphorylation-independent ubiquitylation and endocytosis of Fcg receptors. J. Biol. Chem. 281 :33242-33249.

Steinberg, B.E., Scott, C.C. and Grinstein, S. (2006) High-throughput assays of phagocytosis, phagosome maturation and bacterial invasion. Am. J. Physiol. 292: 945-952.

Smith, A.C., Heo, W.D., Braun, V., Jiang, X., Macrae, C., Casanova, J.E., Scidmore, M.A., Grinstein, S., Myer, T. and Brumell, J.H. (2007) A network of Rab GTPases controls phagosome maturation and is modulated by Salmonella enterica serovar typhimurium. J. Cell Biol. 176 :263-268.

Mason, D., Mallo, G.V., Terebiznik, M.R., Payrastre, B., Finlay, B.B., Brumell, J.H. and Grinstein, S. (2007) Alteration of epithelial structure and function associated with PtdIns(4,5)P 2 degradation by a bacterial phosphatase. J. Gen. Physiol. 129 :267-283.

Huynh, K.K., Eskelinen, E-L., Scott, C.C., Malevanets, A., Saftig, P. and Grinstein, S. (2007) LAMP proteins are required for fusion of lysosomes with phagosomes. EMBO J. 26 (2): 313-324.

Lee, W.L., Cosio, G., Ireton, K., and Grinstein, S, (2007) Role of CrkII in Fcg receptor-mediated phagocytosis. J. Biol. Chem. 282 (15): 1135-1143.

Steinberg, B.E., Touret, N., Vargas-Caballero, M. and Grinstein, S. (2007) In situ measurement of the electrical potential across the phagosomal membrane using FRET. Conribution to the proton-motive force. Proc. Natl. Acad. Sci. USA 104: 9523-8.

Lee, W.L., Mason, D., Schreiber, A, and Grinstein, S, (2007) Quantitative analysis of membrane remodeling at the phagocytic cup. Mol. Biol. Cell 8 :2883-2892.

Yeung, T. and Grinstein, S. (2007) Lipid signaling and the modulation of surface charge during phagocytosis. Immunol. Rev. 219 :17-36.

Steinberg , B.E. and Grinstein S. (2007) Unconventional roles of the NADPH oxidase: signaling, ion homeostasis, and cell death. Science STKE 379 :11.

Trimble, W.S. and Grinstein, S. (2007) TB or not TB: Calcium regulation in mycobacterial survival. Cell 130 : 12-14.

Huynh, K.H., Kay, J.G., Stow, J.L. and Grinstein, S. (2008) Fusion, fission, and secretion during phagocytosis.Physiology 22 :366-372.

Huang, Y.W., Yan, M., Collins, R.F., Diciccio, J.E., Grinstein, S. and Trimble, W.S. (2008) Mammalian septins are required for phagosome formation. Mol. Biol. Cell 4 :1717-1726.

Fairn, G. and Grinstein, S. (2008) A one-sided signal. Science 320 : 458-60.

Huynh, K. and Grinstein, S. (2008) Phagocytosis: Dynamin's dual role in phagosome biogenesis. Curr. Biol. 18: 563-565.

Jaqaman, K., Loerke, D., Mettlen, M., Kuwata, H., Grinstein, S., Schmid, S.L. and Danuser, G. (2008) Robust single particle tracking in live cell time-lapse sequences. Nature Methods 8 :695-702.

Steinberg, B.E. and Grinstein, S. (2008) Pathogen destruction versus intracellular survival: the roles of lipids as phagosomal fate determinants. J. Clin. Invest. 118 : 2002-2011.

Huynh, K.K., Gershenzon, E. and Grinstein, S. (2009) Cholesterol accumulation by macrophages impairs phagosome maturation. J. Biol. Chem. 283 :35745-35755.

Li, X.J., Tian, W., Stull, N.D., Grinstein, S., Atkinson, S. and Dinauer, M.C. (2009) A fluorescently tagged C-terminal fragment of p47 phox detects NADPH oxidase dynamics during phagocytosis. Mol. Biol. Cell 20 :1520-1532.

Huang, J., Canadien, V., Lam, G.Y., Steinberg, B.E., Dinauer, M.C., Magalhaes, M.A.O., Glogauer, M., Grinstein, S. and Brumell, J.H. (2009) Activation of antibacterial autophagy by NADPH oxidases. Proc. Nat. Acad. Sci. USA 106 : 6226-6231.

Wang, Y., Roche, O., Yan, M.S., Finak, G., Evans, A.J., Metcalf, J.L., Hast, B.E., Hanna, S.C., Wondergem, B., Furge, K.A., Irwin, M.S., Kim, W.Y., Teh, B.T., Grinstein, S., Park, M., Marsden, P.A. and Ohh, M. (2009) Regulation of endocytosis via the oxygen-sensing pathway . Nature Med. 15: 319-324.

Flannagan, R.S., Cosio, G. and Grinstein, S. (2009) Antimicrobial mechanisms of phagocytes and bacterial evasion strategies. Nature Rev. Microbiol. 7 :355-366.

Huang, J., Canadien, V., Lam, G.Y., Steinberg, B.E., Dinauer, M.C., Magalhaes, M.A.O., Glogauer, M., Grinstein, S. and Brumell, J.H. (2009) Activation of antibacterial autophagy by NADPH oxidases. Proc. Nat. Acad. Sci. USA 106 : 6226-6231.

Yeung, T., Heit ,B., Dubuisson, J.F., Fairn, G.D., Chiu, B., Inman, R., Kapus, A., Swanson, M. and Grinstein, S. (2009) Contribution of phosphatidylserine to membrane surface charge and protein targeting during phagosome maturation. J. Cell Biol. 185 : 917-928.

Fairn, G.D., Ogata, K., Botelho, R.J., Stahl, P.D., Anderson, R.A., DeCamilli, P., Meyer, T., Wodak, S. and Grinstein, S. (2009) An Electrostatic switch displaces phosphatidylinositol phosphate kinases from the membrane during phagocytosis. J. Cell Biol. 187 : 701-714.

Lee, H.K., Mattei, L.M., Steinberg, B.E., Alberts, P., Lee, Y.H., Chervonsky, A., Mizushima, N., Grinstein, S. and Iwasaki, A. (2010) In vivo requirement for Atg5 in antigen presentation by dendritic cells. Immunity 32 : 227-239.

Botelho, R.J. and Grinstein, S. (2011) Phagocytosis. Curr. Biol. 21(14): R533-538.

Bohdanowicz, M. and Grinstein, S. (2010) Vesicular traffic: a Rab SANDwich. Curr. Biol. 20 : R311-314.

Jaqaman, K., Kuwata, H., Touret, N., Collins, R., Trimble, W.S., Danuser, G. and Grinstein, S. (2011) Cytoskeleton-control of CD36 diffusion promotes its receptor and signaling function. Cell 146(4): 593-606.

Fairn, G.D., Hermansson, M., Somerharju, P. and Grinstein, S. (2011) Phosphatidylserine polarization is required for proper Cdc42 localization and for development of cell polarity. Nature Cell Biol. (in press)

Department of Biochemistry
University of Toronto
Toronto, Canada

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Last Modified: 21 December, 2011 9:31 AM