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Mechanochemical mechanism underlying intercellular Ca2+ wave propagation and its crucial role in apoptotic cell extrusion

Author

Listed:
  • Sohei Yamada

    (8916-5 Takayama
    3 Bunkyo-Cho)

  • Ryohei Yasukuni

    (8916-5 Takayama
    5-16-1 Omiya)

  • Yasumasa Bessho

    (8916-5 Takayama
    8916-5 Takayama)

  • Yasuyuki Fujita

    (Kyoto University)

  • Yoichiroh Hosokawa

    (8916-5 Takayama
    8916-5 Takayama)

  • Takaaki Matsui

    (8916-5 Takayama
    8916-5 Takayama
    8916-5 Takayama)

Abstract

Calcium (Ca2+) wave propagation plays a crucial role in intercellular communication. Elevation of cytosolic Ca2+ (Ca2+ transient) in a single cell is attributed to various Ca2+ channels present in the plasma membrane and endoplasmic reticulum, whereas gap junctions contribute to propagation of Ca2+ waves between cells. However, we found that Ca2+ waves propagate without gap junctions during apoptotic cell extrusion (ACE). Mechanistically, we identified that a chain reaction of mechano-signal transduction from proximal to distal cells through the mechanosensitive Ca2+ channels (MCCs) mediates the Ca2+ wave propagation; an apoptotic cell shrinks accompanied by a Ca2+ transient, followed by pulling the edges of neighboring cells, which opens MCCs in neighboring cells, resulting in Ca2+ transients in these cells. Furthermore, Ca2+ wave propagation promotes Rac-Arp2/3 pathway-mediated polarized collective migration, generating approximately 1 kPa of force toward extruding cells. Our results uncovered a mechanochemical mechanism of Ca2+ wave propagation and its significant role in ACE.

Suggested Citation

  • Sohei Yamada & Ryohei Yasukuni & Yasumasa Bessho & Yasuyuki Fujita & Yoichiroh Hosokawa & Takaaki Matsui, 2025. "Mechanochemical mechanism underlying intercellular Ca2+ wave propagation and its crucial role in apoptotic cell extrusion," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65474-9
    DOI: 10.1038/s41467-025-65474-9
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    References listed on IDEAS

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