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KRAP tethers IP 3 receptors to actin and licenses them to evoke cytosolic Ca 2+ signals

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Thillaiappan, Nagendra Babu  ORCID logo
Smith, Holly A. 
Atakpa-Adaji, Peace 


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.



Article, /631/45/612/1228, /631/80/86/1999, /631/80/2373/2238, /631/80/128/1276, /631/80/642/1463, /13/109, /13, /13/95, /14, /14/19, /14/35, /96/34, article

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Nature Communications

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Nature Publishing Group UK
Wellcome Trust (Wellcome) (101844)
RCUK | Biotechnology and Biological Sciences Research Council (BBSRC) (BB/T012986/1)