Comparative analysis of single‐molecule dynamics of trpv1 and trpv4 channels in living cells

Yutaro Kuwashima, Masataka Yanagawa, Mitsuhiro Abe, Michio Hiroshima, Masahiro Ueda, Makoto Arita, Yasushi Sako

Research output: Contribution to journalArticlepeer-review

Abstract

TRPV1 and TRPV4, members of the transient receptor potential vanilloid family, are multimodal ion channels activated by various stimuli, including temperature and chemicals. It has been demonstrated that TRPV channels function as tetramers; however, the dynamics of the diffusion, oligomerization, and endocytosis of these channels in living cells are unclear. Here we undertook single‐molecule time‐lapse imaging of TRPV1 and TRPV4 in HEK 293 cells. Differences were observed between TRPV1 and TRPV4 before and after agonist stimulation. In the resting state, TRPV4 was more likely to form higher‐order oligomers within immobile membrane domains than TRPV1. TRPV1 became immobile after capsaicin stimulation, followed by its gradual endocytosis. In contrast, TRPV4 was rapidly internalized upon stimulation with GSK1016790A. The selective loss of immobile higher‐order oligomers from the cell surface through endocytosis increased the proportion of the fast‐diffusing state for both subtypes. With the increase in the fast state, the association rate constants of TRPV1 and TRPV4 increased, regenerating the higher‐order oligomers. Our results provide a possible mechanism for the different rates of endocytosis of TRPV1 and TRPV4 based on the spatial organization of the higher‐order structures of the two TRPV channels.

Original languageEnglish
Article number8473
JournalInternational journal of molecular sciences
Volume22
Issue number16
DOIs
Publication statusPublished - 2021 Aug

Keywords

  • Diffusion
  • Endocytosis
  • Receptor oligomerization
  • Single‐molecule imaging
  • TRPV channel

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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