Subcellular localization and endocytic function of low density lipoprotein receptor-related protein in human glioblastoma cells

Guojun Bu, Esther A. Maksymovitch, Hans Geuze, Alan L. Schwartz

Research output: Contribution to journalArticle

122 Scopus citations

Abstract

The low density lipoprotein receptor-related protein (LRP) is a multifunctional cell surface receptor that binds and endocytoses several structurally and functionally distinct ligands. Several of the ligands for LRP participate in both normal physiology and pathophysiology of the central nervous system. To begin to gain insights into the role of LRP in the central nervous system, we have analyzed the expression, subcellular distribution, and endocytic function of LRP in human glioblastoma U87 cells. These cells express an abundance of LRP at both the mRNA and protein levels. A 39-kDa protein, which copurifies with LRP and regulates its ligand binding activity, is also highly expressed in U87 cells. The subcellular localization of LRP and the 39-kDa protein was analyzed using scanning laser confocal and electron microscopy combined with immunolabeled U87 cells. At the plasma membrane, LRP was largely confined to clathrin-coated pits. Within cells, LRP and the 39-kDa protein partially colocalized within rough endoplasmic reticulum and the Golgi complex, suggesting a potential intracellular interaction between the two proteins. Little 39-kDa protein was found in endosomes in which LRP occurred abundantly. In examining the functional role of LRP in U87 cells, we found that LRP at the cell surface and along the cellular processes was functional in the binding and endocytosis of its ligands, and its activity therein was regulated by the 39-kDa protein. Using truncated recombinant 39-kDa protein constructs, we also demonstrated that distinct regions of the 39-kDa protein were responsible for inhibiting the binding of different LRP ligands on U87 cells. Our results thus strongly suggest several potential roles for LRP in brain protein and lipoprotein metabolism, as well as control of extracellular protease activity.

Original languageEnglish (US)
Pages (from-to)29874-29882
Number of pages9
JournalJournal of Biological Chemistry
Volume269
Issue number47
StatePublished - Nov 25 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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