William S. Trimble Professor

Ph.D., Toronto, 1987

Hospital for Sick Children, Division of Cell Biology, McMaster Building, Room 4004A

Regulation of Cell Division and Secretion

Research Synopsis

Role of septins in cell division .
A major focus of our research in recent years has been to elucidate the functions of a family of cytoskeletal, filamentous GTPases called septins . Septins are essential for the final step in the cell cycle, cytokinesis, in a wide variety of organisms from yeast to man. Current work in the laboratory is aimed at determining how they are regulated, defining their role in cytokinesis, and determining what other cellular processes they may regulate. They have diverse functions as diffusion barriers and multi-molecular scaffolds. In addition, we have found that septins regulate exocytosis in the brain at least part of their function in cytokinesis may be to mediate the fusion of membranes necessary for the division of cells.

Molecular mechanisms of membrane fusion.
Research in my laboratory has had a longstanding interest in understanding the mechanisms that control the fusion of intracellular membranes. Such fusion events are responsible for everything from the secretion of neurotransmitters in the brain and release of hormones into the bloodstream, to the maintenance of organelle structure. Specifically, we are examining the SNARE proteins, which are thought to control the docking and fusion of secretory vesicles with the plasma membrane. These proteins, VAMP, syntaxin, and SNAP-23/25 form a stable complex which is disassembled by action of the soluble proteins SNAP and NSF. More recent work has focused on the AAA ATPase NSF and its regulation within the brain.

Role of Membrane and cytoskeletal proteins in innate immune responses
Another area of research in my laboratory involves study of the dynamic properties of membrane and cytoskeletal components in the innate immune response. Specifically, we have focused on the scavenger receptor CD36 to investigate its organization, mobility and signaling properties in the context of pathogen or OxLDL uptake.


Selected Publications

Tsang, CW, MP Estey, JE DiCiccio, H Xie, D Patterson and WS Trimble (2011) Characterization of presynaptic septin complexes in mammalian hippocampal neurons. Biol. Chem. 392:739-49.

Estey, MP, MS Kim and WS Trimble (2011) The septins . Curr. Biol. 21: R384-387.

Jaqaman, K, H Kuwata, N Touret, R. Collins, W Trimble , G Danuser and S Grinstein. (2011) The cytoskeleton reduces the diffusional dimensionality of CD36 promoting its aggregation and signaling. Cell 146:593-606.

Estey, MP, C DiCiano-Oliveira, MT Bejide, CD Froese, and WS Trimble (2010) Distinct roles of septins in cytokinesis: SEPT9 regulates exocyst localization during abscission. J. Cell Biol. 191:741-749.

Yang, Y-M, M Fedchyshyn, G. Grande, J Aitoubah, CW Tsang, H. Xie, C.A. Ackerley, WS Trimble* and L-Y Wang* (2010) Septins regulate developmental switching from microdomain to nanodomain coupling of Ca 2+ influx to neurotransmitter release at a central synapse. Neuron 67:100-115 (*co-corresponding authors).

Collins, RF, N Touret, H Kuwata, NN Tandon, S Grinstein and WS Trimble. (2009) Uptake of oxLDL by CD36 occurs by a novel pathway distinct from macropinocytosis. J. Biol. Chem. 284 :   30288 - 30297.

Tooley, AJ, J. Gilden, J Jacobelli, P Beemiller, WS Trimble , M Kinoshita and MF Krummel (2009) The septin cytoskeleton is essential for cortical integrity and persistent motility in amoeboid T lymphocytes. Nature Cell Biol. 11:17-26.

Tsang, CW, M Fedchyshyn, J Harrison, H Xie, J Xue, PJ Robinson, L-Y Wang and WS Trimble (2008) Superfluous role of mammalian septins 3 and 5 in neuronal development and synaptic transmission. Mol. Cell. Biol. 28:7012-7029.

Huang, YW, M Yan, RF Collins, JE DiCiccio, S Grinstein and WS Trimble (2008) Mammalian septins are required for phagosome formation. Mol. Biol. Cell 19 1717-1726.

Joo, E, MC Surka and WS Trimble (2007) Mammalian Sept2 is required for scaffolding non-muscle myosin II and its kinases. Developmental Cell 13:677-690.

Trimble, WS and S Grinstein (2007) TB or not TB: calcium regulation in mycobacterial survival. Cell 130:12-4.

Yan, M, C DiCiano-Oliveira, S Grinstein and WS Trimble (2007) Coronin function is required for chemotaxis and phagocytosis in human neutrophils. J. Immunol. 178:5769-78.

Steels, J and WS Trimble (2006) Resolving Polarized Views: Septins do the twist. Developmental Cell 11: 591-592.

Yan, M., RF Collins, S Grinstein and WS Trimble (2005) Coronin1 is required for phagocytosis in RAW cells. Mol. Biol. Cell 16 : 3077-87.

Huynh, H., N. Bottini, S. Williams, V. Cherepanov, L. Musumeci, K. Saito, S. Bruckner, E. Vachon, X. Wang, J. Kruger, C-W Chow, M. Pellecchia, E. Monosov, P. Greer, W. Trimble , G. Downey and T. Mustelin (2004) Control of vesicle fusion by a tyrosine phosphatase. Nature Cell Biol . 6 : 831-839.


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