KRAP tethers IP<sub>3</sub> receptors to actin and licenses them to evoke cytosolic Ca<sup>2+</sup> signals.
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Thillaiappan, N. B., Smith, H. A., Atakpa-Adaji, P., & Taylor, C. (2021). KRAP tethers IP<sub>3</sub> receptors to actin and licenses them to evoke cytosolic Ca<sup>2+</sup> signals.. Nature communications, 12 (1), 4514. https://doi.org/10.1038/s41467-021-24739-9
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.
Hela Cells, Cytosol, Animals, Humans, Calcium, Microfilament Proteins, Actins, Membrane Proteins, Microscopy, Fluorescence, RNA Interference, Protein Binding, Inositol 1,4,5-Trisphosphate Receptors, HEK293 Cells
Emmanuel College Cambridge
Wellcome Trust (101844/Z/13/Z)
External DOI: https://doi.org/10.1038/s41467-021-24739-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/326833
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