Class A Scavenger Receptor-mediated Adhesion and Internalization Require Distinct Cytoplasmic Domains

Ninetta Kosswig, Stuart Rice, Alan Daugherty, Steven R. Post

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Class A scavenger receptors (SR-A) are transmembrane glycoproteins that mediate both ligand internalization and cell adhesion. Previous studies have identified specific amino acids in the cytoplasmic tail of SR-A that regulate receptor internalization; however, the role of cytoplasmic domains in regulating cell adhesion has not been addressed. To investigate the role of cytoplasmic domains in SR-A-mediated adhesion and to address whether SR-A-mediated adhesion and internalization require distinct cytoplasmic domains, different SR-A constructs were stably expressed in human embryonic kidney (HEK 293) cells. Deleting the entire cytoplasmic tail (SR-AΔ1-55) greatly reduced receptor protein abundance. Retaining the six amino acids proximal to the membrane (SR-AΔ1-49) restored receptor protein abundance. Although SR-AΔ1-49 localized to the cell surface, cells expressing this receptor failed to internalize the ligand acetylated low density lipoprotein. Replacing the cytoplasmic tail of SR-A with that of the transferrin receptor (TfR/SR-A) resulted in retention of the chimeric receptor in the endoplasmic reticulum suggesting a specific role for the membrane-proximal amino acids in trafficking SR-A from the endoplasmic reticulum to the Golgi. Like SR-A expressing cells, cells expressing SR-A Δ1-49 displayed increased spreading and adhesion, demonstrating that the membrane-proximal amino acids were sufficient for SR-A-mediated cell adhesion. Together, our results indicate a critical role for the membrane-proximal amino acids in SR-A trafficking and demonstrate that SR-A-mediated adhesion and internalization require distinct cytoplasmic domains.

Original languageEnglish
Pages (from-to)34219-34225
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number36
DOIs
StatePublished - Sep 5 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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