KRAP tethers IP3 receptors to actin and licenses them to evoke cytosolic Ca2+ signals
Nagendra Babu Thillaiappan, Holly Smith, Peace Atakpa‐Adaji, Colin W. Taylor
Abstract
Abstract Regulation of IP 3 receptors (IP 3 Rs) by IP 3 and Ca 2+ allows regenerative Ca 2+ signals, the smallest being Ca 2+ puffs, which arise from coordinated openings of a few clustered IP 3 Rs. Cells express thousands of mostly mobile IP 3 Rs, yet Ca 2+ puffs occur at a few immobile IP 3 R clusters. By imaging cells with endogenous IP 3 Rs tagged with EGFP, we show that KRas-induced actin-interacting protein (KRAP) tethers IP 3 Rs to actin beneath the plasma membrane. Loss of KRAP abolishes Ca 2+ puffs and the global increases in cytosolic Ca 2+ concentration evoked by more intense stimulation. Over-expressing KRAP immobilizes additional IP 3 R clusters and results in more Ca 2+ puffs and larger global Ca 2+ signals. Endogenous KRAP determines which IP 3 Rs will respond: it tethers IP 3 R clusters to actin alongside sites where store-operated Ca 2+ entry occurs, licenses IP 3 Rs to evoke Ca 2+ puffs and global cytosolic Ca 2+ signals, implicates the actin cytoskeleton in IP 3 R regulation and may allow local activation of Ca 2+ entry.