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KRAP tethers IP3 receptors to actin and licenses them to evoke cytosolic Ca2+ signals

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Listed:
  • Nagendra Babu Thillaiappan

    (Tennis Court Road
    Qatar University)

  • Holly A. Smith

    (Tennis Court Road)

  • Peace Atakpa-Adaji

    (Tennis Court Road)

  • Colin W. Taylor

    (Tennis Court Road)

Abstract

Regulation of IP3 receptors (IP3Rs) by IP3 and Ca2+ allows regenerative Ca2+ signals, the smallest being Ca2+ puffs, which arise from coordinated openings of a few clustered IP3Rs. Cells express thousands of mostly mobile IP3Rs, yet Ca2+ puffs occur at a few immobile IP3R clusters. By imaging cells with endogenous IP3Rs tagged with EGFP, we show that KRas-induced actin-interacting protein (KRAP) tethers IP3Rs to actin beneath the plasma membrane. Loss of KRAP abolishes Ca2+ puffs and the global increases in cytosolic Ca2+ concentration evoked by more intense stimulation. Over-expressing KRAP immobilizes additional IP3R clusters and results in more Ca2+ puffs and larger global Ca2+ signals. Endogenous KRAP determines which IP3Rs will respond: it tethers IP3R clusters to actin alongside sites where store-operated Ca2+ entry occurs, licenses IP3Rs to evoke Ca2+ puffs and global cytosolic Ca2+ signals, implicates the actin cytoskeleton in IP3R regulation and may allow local activation of Ca2+ entry.

Suggested Citation

  • Nagendra Babu Thillaiappan & Holly A. Smith & Peace Atakpa-Adaji & Colin W. Taylor, 2021. "KRAP tethers IP3 receptors to actin and licenses them to evoke cytosolic Ca2+ signals," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24739-9
    DOI: 10.1038/s41467-021-24739-9
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    Cited by:

    1. Máté Katona & Ádám Bartók & Zuzana Nichtova & György Csordás & Elena Berezhnaya & David Weaver & Arijita Ghosh & Péter Várnai & David I. Yule & György Hajnóczky, 2022. "Capture at the ER-mitochondrial contacts licenses IP3 receptors to stimulate local Ca2+ transfer and oxidative metabolism," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Iqbal Dulloo & Peace Atakpa-Adaji & Yi-Chun Yeh & Clémence Levet & Sonia Muliyil & Fangfang Lu & Colin W. Taylor & Matthew Freeman, 2022. "iRhom pseudoproteases regulate ER stress-induced cell death through IP3 receptors and BCL-2," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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