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.

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 #
5R29NS035122-05
Application #
6393790
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Finkelstein, Robert
Project Start
1997-09-30
Project End
2003-05-31
Budget Start
2001-06-01
Budget End
2003-05-31
Support Year
5
Fiscal Year
2001
Total Cost
$106,694
Indirect Cost
Name
University of Virginia
Department
Pathology
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904