Properties of rat melanin-concentrating hormone receptor 1 internalization

Yumiko Saito, Mitsue Tetsuka, Yue Li, Hitoshi Kurose, Kei Maruyama

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Melanin-concentrating hormone (MCH) is a neuropeptide that plays an important role in several physiological processes. It activates two G protein-coupled receptors (GPCRs), MCH1R and MCH2R, of which MCH1R seems to be a key regulator of food intake. By using HEK293T cells stably transfected with Flag-tagged rat MCH1R, we investigated the mechanism underlying the MCH-induced internalization pathway, which is important for the desensitization or regulation of the receptor response. Quantitative analysis by flow cytometry indicated that the rate of MCH1R internalization progressed in a rapid and time-dependent manner during the first 30 min, and was partly inhibited by pretreatment with the selective protein kinase C (PKC) inhibitor Go6850. Overexpression of dominant-negative β-arrestin-2 (284-409) or dynamin I-K44 A significantly prevented MCH-induced internalization of MCH1R, while overexpression of dominant-negative β-arrestin-1-V53 D had no effect. A triple-substituted mutant at Thr317, Ser325 and Thr 342 to Ala residue in the C-terminus significantly prevented MCH-induced receptor internalization. Similar extents of internalization prevention were noted with the deletion mutants ΔThr342 and ΔGlu346, lacking 11 and 7 residues in the C-terminal tail, respectively. Our data suggest that MCH1R undergoes rapid MCH-induced internalization through a PKC-, β-arrestin-2- and dynamin I-dependent pathway and that a portion of the C-terminal tail plays an important role in the internalization process.

Original languageEnglish
Pages (from-to)1597-1604
Number of pages8
JournalPeptides
Volume25
Issue number10 SPEC. ISS.
DOIs
Publication statusPublished - Oct 2004

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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