C-terminus of PIEZO1 governs Ca 2+ influx and intracellular ERK1/2 signaling pathway in mechanotransduction.

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  • Additional Information
    • Source:
      Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
    • Publication Information:
      Publication: <2002- >: San Diego, CA : Elsevier
      Original Publication: New York, Academic Press.
    • Subject Terms:
      MAP Kinase Signaling System* ; Mechanotransduction, Cellular*/physiology; Humans ; Mice ; Animals ; Calcium/metabolism ; HEK293 Cells ; Signal Transduction ; Ion Channels/metabolism ; Calcium, Dietary
    • Abstract:
      Cells sense and respond to extracellular mechanical stress through mechanotransduction receptors and ion channels, which regulate cellular behaviors such as cell proliferation and differentiation. Among them, PIEZO1, piezo-type mechanosensitive ion channel component 1, has recently been highlighted as a mechanosensitive ion channel in various cell types including mesenchymal stem cells. We previously reported that PIEZO1 is essential for ERK1/2 phosphorylation and osteoblast differentiation in bone marrow-derived mesenchymal stem cells (BMSCs), induced by hydrostatic pressure loading and treatment with the PIEZO1-specific activator Yoda1. However, the molecular mechanism underlying how PIEZO1 induces mechanotransduction remains unclear. In this study, we investigated that the role of the C-terminus in regulating extracellular Ca 2+ influx and activating the ERK1/2 signaling pathway. We observed the activation of Fluo-4 AM in the Yoda1-stimulated human BMSC line UE7T-13, but not in a calcium-depleted cell culture medium. Similarly, Western blotting analysis revealed that Yoda1 treatment induced ERK1/2 phosphorylation, but this induction was not observed in calcium-depleted cell culture medium. To investigate the functional role of the C-terminus of PIEZO1, we generated HEK293 cells stably expressing the full-length mouse PIEZO1 (PIEZO1-FL) and a deletion-type PIEZO1 lacking the C-terminal intracellular region containing the R-Ras-binding domain (PIEZO1-ΔR-Ras). We found that Yoda1 treatment predominantly activated Flou-4 AM and ERK1/2 in PIEZO1-FL-trasfected cells but neither in PIEZO1-ΔR-Ras-transfected cells nor control cells. Our results indicate that the C-terminus of PIEZO1, which contains the R-Ras binding domain, plays an essential role in Ca 2+ influx and activation of the ERK1/2 signaling pathway, suggesting that this domain is crucial for the mechanotransduction of osteoblastic differentiation in BMSCs.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that might affect the research reported in this paper.
      (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
    • Contributed Indexing:
      Keywords: C-terminus; Ca(2+) influx; ERK signaling pathway; Mechanotransduction; PIEZO1; R-Ras binding domain
    • Accession Number:
      SY7Q814VUP (Calcium)
      0 (Ion Channels)
      0 (Calcium, Dietary)
      0 (PIEZO1 protein, human)
    • Publication Date:
      Date Created: 20231006 Date Completed: 20231101 Latest Revision: 20231105
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.bbrc.2023.09.080
    • Accession Number:
      37801988