George J. Zanazzi

2nd Year Graduate Student

Department: Neurobiology & Behavior

Graduate Program: Neuroscience

Advisor: Dr. Gary Matthews

Abstract:

Title:  Mechanisms of Exocytosis at Tonic Synapses

Fast communication between neurons occurs at synapses, where vesicles in the presynaptic terminal release transmitter onto the target neuron in response to an influx of calcium. Signal propagation is particularly rapid and sustained at the first two synapses in the visual system; i.e., the output synapses of photoreceptors and bipolar cells. The presynaptic terminals of these two neurons tonically release transmitter at active zones containing ribbons, which are proteinaceous organelles that tether vesicles. While the synaptic ribbon is essential for visual function, its precise role in exocytosis is unclear. To track vesicle fusion at retinal ribbon synapses, we have generated transgenic zebrafish that express an optical reporter of exocytosis under the control of either an inducible promoter or a bipolar cell-specific promoter. Ribbons can be marked, in photoreceptors and bipolar cells isolated from these zebrafish, with a fluorescent peptide that binds to a unique component of ribbons called RIBEYE. The roles of specific SNARE complex components at retinal ribbon synapses are currently being studied via knockdown and overexpression approaches. Taken together, these studies aim to characterize cellular and molecular mechanisms of vesicle fusion at tonic synapses in the retina, and may shed light on general mechanisms of exocytosis.

Publications:
(MSTP-supported publications indicated with an *)

*Zanazzi G, Matthews G. (2009). The molecular architecture of ribbon presynaptic terminals. Molec. Neurobiol. In press.

*Zanazzi G, Matthews G. (2007). A doubleheader in endocytosis. Neuron 56:939-942.

Koticha, D., Maurel, P., Zanazzi, G., Kane-Goldsmith, N., Basak, S., Babiarz, J., Salzer, J., Grumet, M. (2006). Neurofascin interactions play a critical role in clustering sodium channels, ankyrin G and beta IV spectrin at peripheral nodes of Ranvier. Devel. Biol. 293:1-12.

Melendez-Vasquez, C., Carey, D.J., Zanazzi, G., Reizes, O., Maurel P., and Salzer, J.L. (2005). Differential expression of proteoglycans at central and peripheral nodes of Ranvier. Glia. 52:301-308.

Taveggia C., Zanazzi, G., Petrylak, A., Yano, H., Rosenbluth, J., Einheber, S., Xu, X., Esper, R., Loeb, J., Shrager, P., Falls, D.L., Chao, M.V., Role, L., and Salzer, J.L. (2005). Type III neuregulin-1 levels determine the ensheathment fate of axons. Neuron. 47:681-694.

Gil, O.D., Zhang, L., Chen, S., Ren, Y.Q., Pimenta, A., Zanazzi, G., Hillman, D., Levitt, P. and Salzer, J.L. (2002). Complementary expression and heterophilic interactions between IgLON family members neurotrimin and LAMP. J. Neurobiol. 51:190-204.

Rambukkana, A., Zanazzi, G., Tapinos, N. and Salzer, J.L. (2002). Contact-dependent induction of demyelination by Mycobacterium leprae in the absence of immune cells. Science. 296:927- 931.

Chen, S., Gil, O.D., Ren, Y.Q., Zanazzi, G., Salzer, J.L. and Hillman, D. (2002). Neurotrimin expression during cerebellar development suggests roles in axon fasciculation and synaptogenesis. J. Neurocytol. 30:927-937.

Lustig M.*, Zanazzi G.*, Sakurai T., Blanco C., Levinson S.R., Lambert S., Grumet M., and Salzer J.L. (2001). Nr-CAM and neurofascin interactions regulate ankyrin G and sodium channel clustering at the node of Ranvier. Curr. Biol. 11:1864-1869. *Equal contribution.

Melendez-Vasquez, C., Rios, J.C., Zanazzi, G., Bretscher, A., Lambert, S. and Salzer, J.L. (2001). Nodes of Ranvier form in association with ERM-positive Schwann cell microvilli. Proc. Natl. Acad. Sci. 98:1235-1240.

Zanazzi, G., Einheber, S., Westreich, R., Hannocks, M.-J., Bedell-Hogan, D., Marchionni, M.A. and Salzer, J.L. (2001). Glial growth factor/neuregulin inhibits myelination and induces demyelination. J. Cell Biol. 152:1289-1299.

Ng, V.*, Zanazzi, G.*, Timpl, R., Talts, I.F., Salzer, J.L., Brennan, P.J. and Rambukkana, A. (2000). Role of the cell wall phenolic glycolipid-1 in the peripheral nerve predilection of Mycobacterium leprae. Cell. 103:511-524. *Equal contribution.

Tikoo, R., Zanazzi, G., Shiffman, D., Salzer, J. and Chao, M.V. (2000). Cell cycle control of Schwann cell proliferation: role of cyclin-dependent kinase-2. J. Neurosci. 20:4627-4634.

Ching, W., Zanazzi, G., Levinson, S.R. and Salzer, J.L. (1999). Clustering of neuronal sodium channels requires contact with myelinating Schwann cells. J. Neurocytol. 28:295-301.

Galbiati, F., Volonte, D., Gil, O., Zanazzi, G., Salzer, J.L., Sargiacomo, M., Scherer, P.E., Engelman, J.A., Schlegel, A., Parenti, M., Okamoto, T. and Lisanti, M.P. (1998). Expression of caveolin-1 and -2 in differentiating PC12 cells and dorsal root ganglion neurons: caveolin-2 is up-regulated in response to cell injury. Proc. Natl. Acad. Sci. 95:10257-10262.

Rambukkana, A., Yamada, H., Zanazzi, G., Mathus, T., Salzer, J.L., Yurchenco, P.D., Campbell, K.P. and Fischetti, V.A. (1998). Role of alpha-dystroglycan as a Schwann cell receptor for Mycobacterium leprae. Science. 282:2076-2079.

Gil, O.D., Zanazzi, G., Struyk, A. and Salzer, J.L. (1998). Neurotrimin mediates bifunctional effects on neurite outgrowth via homophilic and heterophilic interactions. J. Neurosci. 18:9312- 9325.

Einheber, S., Zanazzi, G., Ching, W., Scherer, S., Milner, T.A., Peles, E. and Salzer, J.L. (1997). The axonal membrane protein Caspr/neurexin IV is a component of the septate-like paranodal junctions that assemble during myelination. J. Cell Biol. 139:1495-1506.

Desser, T.S., Rubin, D.L., Muller, H.H., Qing, F., Khodor, S., Zanazzi, G., Young, S.W., Ladd, D.L., Wellons, J.A., Kellar, K.E., Toner, J.L. and Snow, R.A. (1994). Dynamics of tumor imaging with Gd-DTPA-polyethylene glycol polymers: dependence on molecular weight. J. Mag. Res. Imag. 4:467-472.

Young, S.W., Sidhu, M.K., Qing, F., Muller, H.H., Neuder, M., Zanazzi, G., Mody, T.D., Hemmi, G., Dow, W., Mutch, J.D., Sessler, J.L. and Miller R.A. (1994). Preclinical evaluation of gadolinium (III) texaphyrin complex: a new paramagnetic contrast agent for magnetic resonance imaging. Invest. Radiol. 29:330-338.

Publications:
(MSTP-supported publications indicated with an *)

*Zanazzi G, Matthews G. (2009). The molecular architecture of ribbon presynaptic terminals. Molec. Neurobiol. In press.

*Zanazzi G, Matthews G. (2007). A doubleheader in endocytosis. Neuron 56:939-942.

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