Mutations in the exocyst component Sec5 disrupt neuronal membrane traffic, but neurotransmitter release persists.
The exocyst (Sec6/8) complex is necessary for secretion in yeast and has been postulated to establish polarity by directing vesicle fusion to specific sites along the plasma membrane. The complex may also function in the nervous system, but its precise role is unknown. We have investigated exocyst function in Drosophila with mutations in one member of the complex, sec5. Null alleles die as growth-arrested larvae, whose neuromuscular junctions fail to expand. In culture, neurite outgrowth fails in sec5 mutants once maternal Sec5 is exhausted. Using a trafficking assay, we found impairments in the membrane addition of newly synthesized proteins. In contrast, synaptic vesicle fusion was not impaired. Thus, Sec5 differentiates between two forms of vesicle trafficking: trafficking for cell growth and membrane protein insertion depend on sec5, whereas transmitter secretion does not. In this regard, sec5 differs from the homologs of other yeast exocytosis genes that are required for both neuronal trafficking pathways.
Murthy
Mala
M
Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.
Garza
Dan
D
Scheller
Richard H
RH
Schwarz
Thomas L
TL
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002874:Chromosome Mapping; D004330:Drosophila; D005089:Exocytosis / Q000502:physiology*; D016296:Mutagenesis / Q000502:physiology; D016501:Neurites / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism
D018377:Neurotransmitter Agents; C103131:SEC5 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins