Regulation of thromboxane receptor trafficking through the prostacyclin receptor in vascular smooth muscle cells: Role of receptor heterodimerization

Stephen J. Wilson, Jennifer K. Dowling, Lei Zhao, Erin Carnish, Emer M. Smyth

Research output: Contribution to journalArticleResearchpeer-review

43 Citations (Scopus)

Abstract

BACKGROUND - Prostacyclin (PGI2) and thromboxane (TxA2) effect disparate outcomes for atherogenesis and the response to vascular injury; PGI2, a vasodilator and inhibitor of platelet aggregation, limits the deleterious actions of TxA2, a vasoconstrictor and platelet activator. Dimerization of their G protein-coupled receptors, IP and TP, evokes a modified cellular response through which IP/TP counter-balance may be effected. We examined the consequence of IP/TP interaction for the regulatory pathways of both receptors. METHODS AND RESULTS - TPα overexpressed in HEK293 cells or expressed endogenously in aortic smooth muscle cells (ASMCs) was internalized after selective activation of either TP or IP. Homologous trafficking of TP was unaltered by coexpression of IP. Heterologous sequestration of TPα required the physical presence of activated IP, in transfected and native cells, but was independent of IP signaling to adenylyl cyclase. Reciprocal heterologous regulation of IP, via activated TP, was evident in both HEK293 cells and ASMCs. Homologous TP internalization led to receptor retention and degradation. In contrast, when internalization was IP-induced, TPα was recycled to the cell surface in coexpressing HEK293 cells, but not in ASMCs, in accord with the postendocytotic pathway of IP. CONCLUSIONS - IP/TPα interaction permits reciprocal regulation of receptor endocytosis via the trafficking pathway determined by the activated dimeric partner.

Original languageEnglish
Pages (from-to)290-296
Number of pages7
JournalArteriosclerosis, Thrombosis and Vascular Biology
Volume27
Issue number2
DOIs
Publication statusPublished - Feb 2007
Externally publishedYes

Keywords

  • G protein-coupled receptor
  • Heterodimer
  • Internalization
  • Prostacyclin
  • Thromboxane

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