Functional importance of the oligomer formation of the neuropeptide receptor VIPR2

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  • Asano Satoshi
    Dept. of Cell. Mol. Pharmacol., Grad. Sch. of Biomed. Health Sci., Hiroshima Univ. Sch. of Dent., Hiroshima Univ.
  • Ozasa Kairi
    Sch. of Dent., Hiroshima Univ.
  • Nakazawa Takanobu
    Dept. Biosci., Tokyo Univ. of Agr.
  • Waschek A James
    Univ. of California Los Angeles
  • Ago Yukio
    Dept. of Cell. Mol. Pharmacol., Grad. Sch. of Biomed. Health Sci., Hiroshima Univ. Sch. of Dent., Hiroshima Univ.

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Other Title
  • 神経ペプチド受容体VIPR2のオリゴマー化とその機能的意義

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<p>Vasoactive intestinal peptide (VIP) receptor2 (VIPR2) is a member of the class B G-protein-coupled receptors (GPCRs) that possess seven-transmembrane domains. Some GPCRs have been reported to form homodimers, and dimerized GPCRs may have different characteristics from the monomer. We recently demonstrated that VIP-VIPR2 signaling is critically involved in tumorcell migration. Here, we investigated whether VIPR2 forms homodimers and they have a potential role in regulating cell migration. A pull-down assay revealed homodimerization and oligomerization of VIPR2. To identify the dimerization domain of VIPR2, its truncation mutants were generated. The mutant containing transmembrane domains 3 to 4 (TM3-4) or TM5-6 but not TM1-2 and TM7-C terminal region could bound to full-length VIPR2. Transfection of a truncation mutant TM3-7, which contains binding sites of both TM3-4 and TM5-6, caused a reduction in the levels of homodimerized VIPR2 on the cell membrane and slowed down VIP-induced increase in migration rate of MDA-MB-231 breast cancer cells. In contrast, TM3-7 had no effect on total VIPR2 levels on the cell membrane. In conclusion, our results suggest the oligomerized VIPR2 can serve as a functional unit mediating VIP-induced cancer cell migration.</p>

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