Date of Award

Summer 1997

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Program/Concentration

Biomedical Sciences

Committee Director

Bruce W. Tedeschi

Committee Member

Paul F. Aravich

Committee Member

Keith A. Carson

Committee Member

Francis J. liuzzi

Committee Member

Charles W. Morgan

Abstract

The fast axonally transported proteins represent a subset of neuronal proteins that are conveyed anterogradely as secretory vesicle constituents from the perikarya. Although fast transport displays properties consistent with the general secretory pathway, neuronal structure presents special problems which may require modifications of the general pathway. The elucidation of these special modifications is essential for a more complete understanding of neuronal function both in normal and pathological conditions. In order to characterize the fast transported (FT) proteins and to better understand fast transport trafficking, the FT of radiolabeled retinal ganglion cell (RGC) proteins in the adult rat optic pathway was studied. The optic pathway model system afforded the opportunity to delineate FT trafficking in the axon from FT trafficking at pre-synaptic terminals. Radiolabel studies of FT proteins revealed six distinct classes of proteins. The first class of FT proteins were found to have little or no trafficking preference for axons or pre-synaptic terminals. The second class of FT proteins exhibited no compartmental trafficking preference and decreased in specific activity from 4-48 hr post-labeling. Such decrease could suggest rapid turnover of these FT proteins. A third class of FT proteins showed increased specific activity only in the axon compartment at 24 hour post intra-ocular labeling (PIL). A fourth class of FT proteins appeared to be trafficked to both compartments, but with a slower time course than the general FT population. The fifth and sixth classes of proteins represent those proteins that were preferentially localized to the terminal and axon compartments, respectively. Fractionation of synaptosomal membranes revealed that the majority, but not all, of FT proteins were conveyed as integral membrane proteins. Immunoprecipitation revealed the major 35S-methionine labeled protein in the rat optic pathway (SNAP-25) was found to be associated with specific subsets of FT and slow transported (SCb) proteins. In summary, the FT proteins in the rat optic pathway displayed heterogenous transport initiation, kinetics, compartmentation, and intermolecular association. Since axons lack sorting organelles (e.g., Golgi), these results suggest that neurons have evolved complex mechanisms for differential delivery of FT proteins from the perikarya.

Comments

Dissertation submitted to the Faculty of Eastern Virginia Medical School and Old Dominion University in Partial Fulfillment of the Requirement for the Degree of Doctor of Philosophy in Biomedical Sciences.

DOI

10.25777/x0fn-vp66

ISBN

9780591603927

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