Shu-Chan Hsu Associate Professor Rutgers University Cell Biology & Neuroscience Nelson Labs. Mr. D419 Piscataway. NJ 08854 (732) 445-6999 FAX - 5870 hsu@biology.rutgers.edu Visit Dr. Hsu's Lab!

Molecular mechanisms of synaptic development and function

The mammalian brain. composed of 10¹¹ nerve cells with 10¹⁴ precise synaptic interconnections. is an organ of unparalleled complexity. A major challenge in modern neuroscience is to elucidate the mechanisms by which nascent neurons form and maintain this elaborate cellular network. thereby providing critical insights into neural circuit formation during development and repair following injury. A key initial step in the establishment of neuronal network is the outgrowth of neurites. a complex process that requires coordinated cytoskeleton remodeling and vesicle targeting to designated plasma membrane domains. The research goal of our lab is to use a multi-disciplinary approach to define the biochemical events underlying neurite outgrowth. We have identified two protein complexes. the exocyst (rsec6/8) complex and the sep2/4/6/7/8 family. required for promoting and regulating neurite outgrowth. Currently. we are using molecular biological. biochemical. immunochemical. electrophysiological and cell biological techniques to investigate the molecular mechanisms of these two complexes in regulating neurite development. axon/dendritic differentiation and synapse formation. In addition. we are using these two complexes as molecular handles to identify and isolate other protein players in the neurite outgrowth process. Elucidation of the molecular events underlying neurite outgrowth should provide important insights into the regulation of neuronal growth. differentiation and regeneration.

Selected Publications

Oztan, A., Silvis, M., Weisz, O.A., Bradbury, N.A., Hsu, S.C., Goldenring, J.R., Yeaman, C. and Apodaca, G. (2007) Exocyst requirement for endocytic traffic directed toward the apical and basolateral poles of polarized MDCK cells. Mol Biol Cell 18: 3978-3992.

Wang S, Hsu SC. (2006) The molecular mechanisms of the mammalian exocyst complex in exocytosis. Biochem Soc Trans. 34(Pt 5):687-90.

Wang. S.. Liu. Y.. Adamson C.. Valdez G.. Guo Wei and Hsu. S. -C. (2004) The mammalian exocyst complex. a macromolecule necessary for Golgi-to-plasma membrane protein targeting. inhibits tubulin polymerization. J. Biol. Chem. 279: 35958-35966.

Hsu. S. -C.. Abraham. M.. TerBush D.. and Guo. W. (2004). Role of the exocyst complex in polarized secretion. International Review of Cytology: A Survey of Cell Biology 233: 243-265.

Hsu SC. TerBush D. Abraham M. Guo W. (2004) The exocyst complex in polarized exocytosis. Int Rev Cytol. 233:243-65.

Vega I. and Hsu. S.-C. (2003) The septin filaments associate with the Exocyst complex. microtubules and actin filaments. and play a role in polarized growth upon cell differentiation. Neuroreport 14: 31-37

Wang S. Hsu SC. (2003) Immunological characterization of exocyst complex subunits in cell differentiation. Hybrid Hybridomics. 22(3):159-64.

Schjott JM. Hsu SC. Plummer MR. (2003) The neuronal beta 4 subunit increases the unitary conductance of L-type voltage-gated calcium channels in PC12 cells. J Biol Chem. 278(36):33936-42.

Riefler GM. Balasingam G. Lucas KG. Wang S. Hsu SC. Firestein BL. (2003) Exocyst complex subunit sec8 binds to postsynaptic density protein-95 (PSD-95): a novel interaction regulated by cypin (cytosolic PSD-95 interactor). Biochem J. 373(Pt 1):49-55.

Vega IE. Hsu SC. (2003) The septin protein Nedd5 associates with both the exocyst complex and microtubules and disruption of its GTPase activity promotes aberrant neurite sprouting in PC12 cells. Neuroreport. 14(1):31-7.

Macara IG. Baldarelli R. Field CM. Glotzer M. Hayashi Y. Hsu SC. Kennedy MB. Kinoshita M. Longtine M. Low C. Maltais LJ. McKenzie L. Mitchison TJ. Nishikawa T. Noda M. Petty EM. Peifer M. Pringle JR. Robinson PJ. Roth D. Russell SE. Stuhlmann H. Tanaka M. Tanaka T. Trimble WS. Ware J. Zeleznik-Le NJ. Zieger B. (2002) Mammalian septins nomenclature. Mol Biol Cell 13:4111-4113.

Vega. IE and Hsu. S-C. (2001) The exocyst complex associates with microtubules to mediate vesicle targeting and neurite outgrowth. J. Neurosci. 21 3839-3848.

Hsu. S.-C.. Hazuka. C.D.. Foletii. D.L.. and Scheller. R.H. (1999). Targeting vesicles to specific sites on the plasma membrane: the role of the sec6/8 complex. Trends Cell Biol. 9:150-153

Hsu. S.C.. Hazuka. C. D.. Roth. R.. Foletti. D. L.. Heuser. J.. and Scheller. R. H. (1998.) Subunit composition. protein interactions. and structures of the mammalian brain sec6/8 complex and septin filaments. Neuron 20: 1111-22.

Grindstaff. K.K.. Yeaman. C.. Anandasabapathy. N.. Hsu. S. C.. Rodriguez-Boulan. E.. Scheller. R. H.. and Nelson. W. J. (1998). Sec6/8 complex is recruited to cell-cell contacts and specifies transport vesicle delivery to the basal-lateral membrane in epithelial cells. Cell 93: 731-40.

Hazuka. C.D.. Hsu. S.C. and Scheller. R.H. (1997). Characterization of a cDNA encoding a subunit of the rat brain rsec6/8 complex. Gene 187: 67-73.

Hsu. S.-C.. Ting. A.E.. Hazuka. C.D.. Davanger. S.. Kenny. J.W.. Kee. Y.. and Scheller. R.H. (1996). The mammalian brain rsec6/8 complex. Neuron 17: 1209-1219.