Macrophage colony-stimulating factor differentially regulates low density lipoprotein and transferrin receptors

Liqin Du, Steven R. Post

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Endocytosis mediated by both LDL receptors (LDLRs) and transferrin receptors (TfRs) occurs in clathrin-coated pits and requires specific tyro-sine-based internalization sequences located in the cytoplasmic domain of these receptors. Internalization of these receptors is mediated by endocytic proteins that interact with the internalization domains. We previously showed that macrophage colony-stimulating factor (M-CSF) rapidly increases LDLR-dependent uptake and metabolism of LDL. To study the mechanism by which M-CSF regulates LDL uptake, we compared the effect of M-CSF on the internalization of LDL and transferrin (Tf). Our results show that M-CSF substantially increased the rate of LDLR internalization without increasing LDLR localization on the cell surface. In contrast, M-CSF treatment of macrophages rapidly increased the localization of TfR to the cell surface but did not alter the relative rate of Tf internalization. Moreover, M-CSF regulated TfR and LDLR via the activation of distinct signaling pathways. Recruitment of TfR to the cell surface was attenuated by phosphatidylinositol 3-kinase inhibitors, whereas stimulated LDL uptake was inhibited by the serine/threonine phosphatase inhibitor okadaic acid. Taken together, our results indicate that M-CSF differentially regulates receptors that undergo endocytosis and that increased LDL uptake results from a selective increase in the rate of LDLR internalization.

Original languageEnglish (US)
Pages (from-to)1733-1740
Number of pages8
JournalJournal of lipid research
Volume45
Issue number9
DOIs
StatePublished - Sep 2004

Keywords

  • Clathrin
  • Endocytosis
  • Lipoprotein
  • Metabolism
  • Signaling

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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