Abstract

): The goal of this project is to elucidate the mechanisms of synaptic transmission using Drosophila genetics. The application has two aims.
The first aim i s to examine the role of exocyst, a protein complex essential for proper exocytosis and transport of vesicles. By using mutations in Dsec5, the Drosophila homolog of one of the exocyst proteins, the application seeks to understand the significance of exocyst for membrane trafficking in a multicellular organism. In particular, it seeks to determine whether the complex is needed for the development of a synapse and whether it is continuously required for synapse function.
The second aim i s to conduct a large-scale mutant screen for new genes that may be important for synaptic transmission. The investigator has developed a novel screen (using heterozygous flies with homozygous mutant eyes) in which strong candidates can be identified efficiently. These mutants will be categorized as to the nature of their defects, and those that appear to be most directly related to synaptic transmission will be characterized further. It is expected that the screen should uncover new proteins that influence the synapse and should also yield mutations in biochemically identified proteins for which little functional data are now available.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS041062-03
Application #
6540380
Study Section
Special Emphasis Panel (ZRG1-MDCN-7 (01))
Program Officer
Nichols, Paul L
Project Start
2000-04-01
Project End
2005-03-31
Budget Start
2002-04-01
Budget End
2003-03-31
Support Year
3
Fiscal Year
2002
Total Cost
$395,000
Indirect Cost

  Institution

Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Lee, GaYoung; Schwarz, Thomas L (2016) Filamin, a synaptic organizer in Drosophila, determines glutamate receptor composition and membrane growth. Elife 5:
Teodoro, Rita O; Pekkurnaz, Gulçin; Nasser, Abdullah et al. (2013) Ral mediates activity-dependent growth of postsynaptic membranes via recruitment of the exocyst. EMBO J 32:2039-55
Murthy, Mala; Teodoro, Rita O; Miller, Tamara P et al. (2010) Sec5, a member of the exocyst complex, mediates Drosophila embryo cellularization. Development 137:2773-83
Higashi-Kovtun, Misao E; Mosca, Timothy J; Dickman, Dion K et al. (2010) Importin-beta11 regulates synaptic phosphorylated mothers against decapentaplegic, and thereby influences synaptic development and function at the Drosophila neuromuscular junction. J Neurosci 30:5253-68
Mosca, Timothy J; Schwarz, Thomas L (2010) The nuclear import of Frizzled2-C by Importins-beta11 and alpha2 promotes postsynaptic development. Nat Neurosci 13:935-43
Mosca, Timothy J; Schwarz, Thomas L (2010) Drosophila Importin-?2 is involved in synapse, axon and muscle development. PLoS One 5:e15223
Kurshan, Peri T; Oztan, Asli; Schwarz, Thomas L (2009) Presynaptic alpha2delta-3 is required for synaptic morphogenesis independent of its Ca2+-channel functions. Nat Neurosci 12:1415-23
Dickman, Dion K; Kurshan, Peri T; Schwarz, Thomas L (2008) Mutations in a Drosophila alpha2delta voltage-gated calcium channel subunit reveal a crucial synaptic function. J Neurosci 28:31-8
Miech, Claudia; Pauer, Hans-Ulrich; He, Xi et al. (2008) Presynaptic local signaling by a canonical wingless pathway regulates development of the Drosophila neuromuscular junction. J Neurosci 28:10875-84
Khodosh, Rita; Augsburger, Adela; Schwarz, Thomas L et al. (2006) Bchs, a BEACH domain protein, antagonizes Rab11 in synapse morphogenesis and other developmental events. Development 133:4655-65

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