个人简介

B.Sc., 1995, Imperial College London, UK; Ph.D., 1999, Universita di Padova, Italy

研究领域

Biochemistry/Molecular Biology

Information is exchanged between neurons at synapses, which are essentially specialized sites of cell-cell adhesion . A mature synapse is defined as an accumulation of synaptic vesicles within the axon, in close apposition to a dendritic membrane studded with receptors (see figure)which are held in place by a submembranous scaffold (Sheng and Kim, 2002) . The formation of such an intercellular structure requires spatially and temporally controlled changes in morphology and molecular content at sites of contacts. Recent advances in subcellular fluorescence microscopy have revealed that this process involves the rapid recruitment and stabilization of both pre- and postsynaptic elements. These studies have shown that major components of the synaptic vesicle and active zone machinery travel in clusters together with other presynaptic proteins, such as calcium channels, and are rapidly recruited to new sites of contact (Ahmari et al., 2000; Zhai et al., 2001; Washbourne et al., 2002) . live ZfOn the postsynaptic side, receptor subunits and components of the scaffold or post-synaptic density (PSD) are recruited separately and with distinct time courses within minutes to hours after initial contact (Friedman et al., 2000; Bresler et al., 2001; Washbourne et al., 2002; Bresler et al., 2004) Despite these advances the basic mechanisms by which synapse formation is induced at discrete locations and by which the molecular machinery is recruited to sites of contact remain elusive. We are currently using both mammalian primary neuronal cultures and zebrafish embryos to investigate molecules that are involved in the mechanisms of synapse formation. Techniques currently employed are live confocal imaging of fluorescently-tagged synaptic components, electron microscopy, biochemistry and molecular biology.

近期论文

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Hoy, J., Haeger, P.A., Constable, J.R.L. Arias, R.J., McCallum, R., Kyweriga, M., Davis, L., Schnell, E., Wehr, M., Castillo, P.E. and Washbourne, P. Neuroligin1 drives synaptic and behavioral maturation through intracellular interactions. In press at Journal of Neuroscience 33(22), 9364-9384 (2013). Easley-Neal, C., Fierro, J., Buchanan, J. and Washbourne, P. Late recruitment of synapsin to nascent synapses is regulated by CDK5. Cell Reports 3, 1199-1212 (2013) Tallafuss, A., Gibson, D., Morcos, P. Li, Y., Seredick, S., Eisen, J. and Washbourne, P. Turning gene function ON and OFF using sense and anti-sense photo-morpholinos in zebrafish. Development 139, 1691-1699 (2012) Phillips, J.B., Blanco-Sanchez, B., Lentz, J.J., Tallafuss, A., Khanobdee, K., Sampath, S., Jacobs, Z.G., Han, P.F., Mishra, M., Titus, T.A., Williams, D.A., Keats, B.J., Washbourne, P. and Westerfield, M. Harmonin (Ush1c) is required in Mueller glial cells for photoreceptor synaptic development and function. Disease Models and Mechanisms 4, 786-800 (2011) Davey, C., Tallafuss, A. and Washbourne, P. Differential expression of neuroligin genes in the nervous system of zebrafish. Developmental Dynamics 239, 703-714 (2010) Hoy, J., Constable, J.R.L., Vicini, S., Fu, Z. and Washbourne, P. SynCAM1 recruits NMDA receptors via protein 4.1B. Molecular and Cellular Neuroscience 42, 466-483 (2009) Pietri, T., Manalo, E., Ryan, J., Saint-Amant, L. and Washbourne, P. Glutamate Drives the Touch Response through a Rostral Loop in the Spinal Cord of Zebrafish Embryos. Developmental Neurobiology 69, 780-795 (2009) Barrow, S.L., Constable, J.R.L., Clark, E., El-Sabeawy, F., McAllister, A.K. and Washbourne, P. Neuroligin1: a cell adhesion molecule that recruits PSD-95 and NMDARs by distinct mechanisms during synaptogenesis. Neural Development 4, 17 (2009) Pietri, T., Easley-Neal, C., Wilson, C. and Washbourne, P. Six cadm/SynCAM genes are expressed in the nervous system of developing zebrafish. Developmental Dynamics 237, 233-246 (2008) REVIEWS: Wright, G. and Washbourne, P. Neurexins, Neuroligins and LRRTMs: synaptic adhesion getting fishy. Journal of Neurochemistry, 117, 765-778 (2011) Tallafuss, A. Constable, J.R.L. and Washbourne, P. Organization of central synapses by adhesion molecules. European Journal of Neuroscience, 32, 198-206 (2010) Washbourne, P. Greasing Transmission: Palmitoylation at the Synapse. Neuron 44, 901-902 (2004) Washbourne, P., Dityatev, A., Scheiffele, P., Biederer, T., Weiner, J.A., Christopherson, K. and El-Husseini, A. Cell Adhesion Molecules in Synapse Formation. J. Neurosci. 24, 9244-9249 (2004)