Targeting of G protein-coupled receptors to the basolateral surface of polarized renal epithelial cells involves multiple, non-contiguous structural signals

Christine Saunders, Jeffrey R. Keefer, Carol Ann Bonner, Lee E. Limbird

Research output: Contribution to journalArticlepeer-review

Abstract

Truncations and chimeras of the α(2A)-adrenergic receptor (α(2A)AR) were evaluated to identify membrane domains responsible for its direct basolateral targeting in Madin-Darby canine kidney cells. An α(2A)AR truncation, encoding transmembrane (TM) regions 1-5, was first delivered basolaterally, but within minutes appeared apically, and at steady-state was primarily lateral in its immunocytochemical localization. A TM 1-5 truncation with the third intracellular loop revealed more intense lateral localization than for the TM 1-5 structure, consistent with the role of the third intracellular loop in α(2A)AR stabilization. Addition of TM 6-7 of A1 adenosine receptor (A1AdoR) to α(2A)ARTM1-5 creates a chimera, α(2A)ARTM1- 5/A1AdoRTM6-7, which was first delivered apically, resulting either from loss of α(2A)AR sorting information in TM 6-7 or acquisition of apical trafficking signals within A1AdoRTM6-7. Evidence that α(2A)ARTM6-7 imparts basolateral targeting information is revealed by the significant basolateral localization of the A1AdoRTM1-5/α(2A)ARTM6-7 and A1AdoRTM1-5/ α(2A)ARTM6- 7+i3 chimeras, in contrast to the dominant apical localization of A1AdoR. These results reveal that sequences within TM 1-5 and within TM 6-7 of the α(2A)AR confer basolateral targeting, providing the first evidence that α(2A)AR basolateral localization is not conferred by a single region but by non-contiguous membrane-embedded or proximal sequences.

Original languageEnglish (US)
Pages (from-to)24196-24206
Number of pages11
JournalJournal of Biological Chemistry
Volume273
Issue number37
DOIs
StatePublished - Sep 11 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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