Store-operated Ca²⁺ entry: Evidence for a secretion-like coupling model

The elusive coupling between endoplasmic reticulum (ER) Ca²⁺ stores and plasma membrane (PM) 'storeoperated' Ca²⁺ entry channels was probed through a novel combination of cytoskeletal modifications. Whereas coupling was unaffected by disassembly of the actin cytoskeleton, in situ redistribution of F-actin into a tight cortical layer subjacent to the PM displaced cortical ER and prevented coupling between ER and PM Ca²⁺ entry channels, while not affecting inositol 1,4,5-trisphosphate-mediated store release. Importantly, disassembly of the induced cortical actin layer allowed ER to regain access to the PM and reestablish coupling of Ca²⁺ entry channels to Ca²⁺ store depletion. Coupling is concluded to be mediated by a physical 'secretion-like' mechanism involving close but reversible interactions between the ER and the PM.