REGULATION OF LRP EXPRESSION AND FUNCTION IN THE CNS

University Of Virginia Charlottesville, Charlottesville VA

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Abstract

LP is an endocytic receptor involved in the trafficking of a variety of proteins/protein complexes that have physiologic relevance in the CNS including PNII, lipoprotein metabolites and activated a2M. Receptor associated protein (RAP) copurifies with LRP and blocks cell surface binding of LRP ligands. Regulation of LRP expression might have important biological roles in the nervous system. LRP is developmentally regulated in neurons. In glial cells, LRP appears to be upregulated in certain reactive states and following neoplastic transformation. The hypotheses of this proposal are that: 1) LP and RAP expression in the CNS are dynamically regulated and differentially regulated in astroglial and neuronal cell types and 2) that LRP plays a role in the control of astroglial migration/invasion. The 3 aims are to 1) demonstrate that EGFR ligands and LPS regulated the expression of LRP and RAP in neural cells 2) determine the effect of EGFR ligands and LPS on LRP promoter activity and define the transcription factors responsible for cell type-specific LRP expression in the CNS, and 3) demonstrate the role of LRP expression on neoplastic astrocyte migration/invasion.