Properties of rat melanin-concentrating hormone receptor 1 internalization

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

Research output: Contribution to journalArticle

21 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 Thr 317 , Ser 325 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 ΔThr 342 and ΔGlu 346 , 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 - Jan 1 2004

Fingerprint

Dynamin I
Arrestin
Protein Kinase C
Tail
Physiological Phenomena
Protein C Inhibitor
Protein Kinase Inhibitors
G-Protein-Coupled Receptors
Neuropeptides
Flow cytometry
Flow Cytometry
Eating
Rats
melanin-concentrating hormone
rat Mch1r protein
Chemical analysis
beta-Arrestin 1

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

Cite this

Properties of rat melanin-concentrating hormone receptor 1 internalization. / Saito, Yumiko; Tetsuka, Mitsue; Li, Yue; Kurose, Hitoshi; Maruyama, Kei.

In: Peptides, Vol. 25, No. 10 SPEC. ISS., 01.01.2004, p. 1597-1604.

Research output: Contribution to journalArticle

Saito, Y, Tetsuka, M, Li, Y, Kurose, H & Maruyama, K 2004, 'Properties of rat melanin-concentrating hormone receptor 1 internalization', Peptides, vol. 25, no. 10 SPEC. ISS., pp. 1597-1604. https://doi.org/10.1016/j.peptides.2004.03.026
Saito, Yumiko ; Tetsuka, Mitsue ; Li, Yue ; Kurose, Hitoshi ; Maruyama, Kei. / Properties of rat melanin-concentrating hormone receptor 1 internalization. In: Peptides. 2004 ; Vol. 25, No. 10 SPEC. ISS. pp. 1597-1604.
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