The Role of Cysteine String Protein for Fast Neurotransmitter Release

University Of Pennsylvania, Philadelphia PA

Investigators

Abstract

Regulated neurotransmitter secretion mediates communication between nerve cells of the nervous system. A "sender" cell encodes its electrical signal into a chemical signal by using a neurotransmitter stored in synaptic vesicles. The neurotransmitter is secreted onto a "receiver" cell, which decodes the signal back into an electrical signal. Neurotransmitter secretion is accomplished by fusing the vesicle membrane with the cell membrane expelling its content. Little is known about the molecular machinery driving vesicle fusion. The goal of this proposal is to investigate these molecular mechanisms and, in particular, the role of cysteine-string protein (CSP). This project will test the hypothesis that CSP may mediate secretion by modulating Ca2+ channels, Ca2+ channel-vesicle linkage, and/or vesicle fusion. This will be achieved by employing genetically manipulated motor nerve terminals of the fruit fly Drosophila as a model system. The extraordinary fast and precise communication of nerve cells is central to understand how the nervous system works - how we perceive, move, feel, learn, and remember. Failure of secretion has a fatal influence on human life. In most cases, the abnormalities are so severe that embryonic development will not proceed. Even subtle defects of neurotransmitter secretion severely impair higher brain functions like learning and memory. CSP has been recently implicated as an important factor during the treatment of manic depression in humans. Thus, the research being conducted has crucial implications on our basic knowledge of neuronal secretion and subsequently on human medicine to detect, to treat, and to possibly prevent neurological disorders.