Inositol 1,4,5-trisphosphate receptors (IP3Rs) are channels that release Ca2+ from internal stores following agonist-stimulated generation of IP3 by phospholipase C. The Ca2+ signal generated can take the form of a variety of complex waves/oscillations, and the intracellular distribution of IP3Rs is thought to influence its spatial and temporal dynamics. Jan Parys and co-workers now reveal that things are even more complicated (see ). They have examined the subcellular positioning of IP3Rs in vascular smooth muscle cells stimulated by the hormone arginine-vasopressin. The authors find that, prior to stimulation,IP3R1 and the SERCA-type Ca2+ pump that refills the stores reside in the perinuclear region. After prolonged stimulation, however,they relocalize to the cytoplasm. Parys and co-workers demonstrate that this relocalization can be blocked by agents that inhibit microtubule dynamics or vesicle trafficking. They also show that it depends on protein kinase C (PKC)and that PKC induces outgrowth of microtubules from the perinuclear region into the cytoplasm. The hormone might therefore stimulate PKC-dependent vesicular transport of Ca2+-store components from the perinuclear region to the cytoplasmic ER as some form of adaptive response.
