PTH/PTH-related protein receptor interacts directly with Tctex-1 through its COOH terminus

Maki Sugai, Masaki Saito, Izumi Sukegawa, Yuriko Katsushima, Yoshitaka Kinouchi, Norimichi Nakahata, Tooru Shimosegawa, Teruyuki Yanagisawa, Jun Sukegawa

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

Abstract

COOH-terminal cytoplasmic domains of G protein-coupled receptors (GPCRs) have been shown to carry determinants that control their cell surface localization, internalization, and recycling. In attempts to seek cellular proteins that mediate these processes of PTH/PTH-related protein receptor (PTHR), one of the class B GPCRs, we have found that Tctex-1, a 14kDa light chain of cytoplasmic dynein motor complex, interacts with the COOH-terminal tail of the receptor. A 34-amino-acid stretch of the receptor responsible for binding to Tctex-1 has a bipartite structure consisting of a motif previously implicated in binding of some proteins to Tctex-1 and a putative new consensus sequence. Site-directed mutations or a 20-amino-acid deletion in the bipartite consensus binding sequence abolished the association of the PTHR COOH terminus with Tctex-1 in vitro. A GFP-fused mutant PTHR impaired in binding to Tctex-1 expressed in MDCK cells showed a decreased rate of internalization in response to PTH compared to that of the wild type.

Original languageEnglish
Pages (from-to)24-31
Number of pages8
JournalBiochemical and biophysical research communications
Volume311
Issue number1
DOIs
Publication statusPublished - 2003 Nov 7
Externally publishedYes

Keywords

  • Dynein
  • Internalization
  • PTH/PTHrP receptor
  • Tctex-1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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