The goal of these studies is the elucidation of the components and mechanisms of synaptic remodeling and synaptic vesicle trafficking. This proposal specifically focuses on (1) the uptake of synaptic material produced during remodeling and (2) the endocytosis or """"""""recycling"""""""" of synaptic vesicle components from the plasma membrane. To study the mechanism of action of the presynaptic neurotoxin taipoxin, which appears to inhibit the recycling of synaptic vesicles, two novel gene products were isolated from rat brain using a taipoxin affinity column. One of these proteins has been named Neuronal Fentraxin, or NF, due to its homology to the serum pentraxins elevated during acute phase response. The second protein has been named Taipoxin-associated Calcium Binding Protein49, or TCBP-49, due to interaction with both taipoxin and calcium.
Specific aims were designed to investigate the hypotheses that (1) NP is part of a neuronal uptake pathway responsible for the clearance of extracellular debris during synaptic development and remodeling and (2) TCBP-49, alone or in conjunction with NP, plays a role in vesicle trafficking in the nerve terminal. A combination of biochemical and immunological approaches, including ligand binding assays, affinity chromatography, immunolocalization, and molecular cloning, will be used to identify and characterize proteins and ligands with which NP and TCBP- 49 interact. This approach will yield insight into the cellular functions of these molecules and has the potential to identify many components of a novel synaptic uptake pathway and-the synaptic trafficking machinery. These processes are essential to the normal development and function of the nervous system and may also be involve the etiology of neurological diseases resulting from synaptic malfunction.
