Store-operated calcium entry: a tough nut to CRAC

Store-operated or capacitative Ca 2+ entry is a prominent feature of many electrically nonexcitable cell types. It is due to Ca 2+ ion permeation pathways in the plasma membrane that are activated after receptor-mediated Ca 2+ release from intracellular stores. Despite hundreds of publications on the topic of store-operated Ca 2+ entry and intense efforts by many dedicated laboratories, neither the molecular nature of the ion permeation pathway nor its activation mechanism is known. Here we review the progress made on the characterization of store-operated currents and the challenges encountered in identifying the molecular components of store-operated Ca 2+ entry.