NEW LIGHT ON TRP AND TRPL

Store-operated Ca2+ entry, a mode of Ca2+ influx activated by depletio n of Ca2+ from the internal stores, has been detected in a wide Variet y of cell types and may be the primary mechanism for Ca2+ entry in non excitable cells. Nevertheless, until recently, no candidate store-oper ated channel (SOC) had been identified molecularly. Through the serend ipity of Drosophila genetics, a candidate SOC, referred to as Transien t Receptor Potential (TRP), has been identified that is essential for the light-induced cation conductance in photoreceptor cells. A combina tion of in vitro and in vivo studies has provided strong evidence that TRP is a bona fide SOC. Moreover, TRP forms a supramolecular complex, proposed to be critical for feedback regulation and/or activation, th at includes rhodopsin, phospholipase C, protein kinase C, calmodulin, and the PDZ domain-containing protein, INAD. INAD seems to be a scaffo lding protein that links TRP with several of these other proteins in t he complex. TRP also complexes with a related channel subunit, TRP-lik e, to form a heteromultimer with conductance characteristics distinct from those of TRP or TRP-like homomultimers. A family of proteins rela ted to TRP is conserved from Caenorhabditis elegans to humans, and rec ent evidence indicates that at least some of these proteins are SOCs. The human TRP-related proteins may mediate many of the store-operated conductances that have been identified previously in a plethora of hum an cells.