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AuthorThillaiappan, Nagendra Babu
AuthorSmith, Holly A.
AuthorAtakpa-Adaji, Peace
AuthorTaylor, Colin W.
Available date2023-08-28T09:09:49Z
Publication Date2021
Publication NameNature Communications
ResourceScopus
ISSN20411723
URIhttp://dx.doi.org/10.1038/s41467-021-24739-9
URIhttp://hdl.handle.net/10576/46835
AbstractRegulation 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. 2021, The Author(s).
SponsorThe authors thank Martyn Reynolds and Stephen Tovey (Cairn, UK) for help with super-resolution confocal microscopy. Supported by a Wellcome Senior Investigator Award (grant no. 101844), and by a grant (grant no. BB/T012986/1) and studentship (to H.A.S) from the Biotechnology and Biological Sciences Research Council UK. P.A.-A. is a research fellow of Emmanuel College, Cambridge.
Languageen
PublisherNature Research
SubjectActin
Calcium signalling
Cytoskeletal proteins
Endoplasmic reticulum
Super-resolution microscopy
TitleKRAP tethers IP3 receptors to actin and licenses them to evoke cytosolic Ca2+ signals
TypeArticle
Issue Number1
Volume Number12
dc.accessType Open Access


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