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Roles of the Growth Arrest-Specific Gene6 (Gas6) in Neuronal Function

$356,045FY2002BIONSF

Indiana University, Bloomington IN

Investigators

Abstract

ABSTRACT The nervous system is mainly composed of two types of cells, neurons and glia. Unlike glia, most neuronal cells lose their ability to divide (proliferate) at an early developmental stage. Therefore neuronal loss is an irreversible process and a major contributor to the impairment of function in the central nervous system (CNS), underscoring the importance of identifying molecules that can decrease neuronal loss. Receptor protein tyrosine kinases (RPTks) are a class of molecules that plays a pivotal role in the survival and proliferation of a large variety of cells. The molecule Gas6 (growth arrest specific gene6), the focus of this study, can bind and activate three related RPTKs, Tyro-3, Axl and Mer. Because Gas6 and Tyro-3 are abundantly expressed in the CNS it is possible that Gas6 acting through Tyro-3 can promote neuronal survival and induce cell proliferation; this is the hypothesis that will be tested. For these studies a combination of morphological and biochemical assays will be used to monitor the survival and proliferative effects of Gas6 on neuroblastoma cells and of neurons obtained from mice in which the Tyro-3 receptor has been genetically inactivated. These studies should help to identify new molecules involved in the promotion of cell survival and proliferation in the CNS, knowledge that may ultimately be used to reduce neuronal loss. .

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