Neurons require cell surface components to link the force- generating cytoskeleton with the extracellular environment to promote neurite outgrowth, fasciculation and the formation and stabilization of synapses. I am studying a specific component of the neuronal cell surface, GP 130, the only known membrane protein that is isolated specifically in association with the neuronal cytoskeleton.
The aims of this research are a) to verify the structure of GP 130 as a transmembrane protein from the sequence of cDNA clones, b) to establish its functional interaction with the neuronal microenvironment and c) to localize GP 130 in the developing and adult nervous system, particularly in synapses. The structure of GP 130 will be derived from the sequence of full- length cDNA clones (Ranscht, in preparation). This will predict the GP 130 insertion into the plasma membrane, glycosylation sites and structural homologies with similar molecules in other cells. The major goal of this proposal is to establish the functional interaction of GP 130 with components of the neuronal microenvironment. To do this, I will develop direct binding assays of GP 130 with extracellular matrix and cellular substrates and attempt to purify the putative ligand by affinity chromatography. My preliminary work suggests that in the embryo, the expression of GP 130 is correlated with neurons reaching the target tissue and, in the adult, GP 130 is accumulated in synapses. To clarify the subcellular localization of GP 130 at synapses, I will conduct ultrastructural immunohistochemical studies of GP 130 in tissue sections of the chicken nervous system. The research I propose will contribute to our understanding of the role of the membrane cytoskeletal linkage in neuronal development and function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29NS025194-03
Application #
3477051
Study Section
Neurology C Study Section (NEUC)
Project Start
1987-07-01
Project End
1992-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
009214214
City
La Jolla
State
CA
Country
United States
Zip Code
92037