Mobile IP₃ receptors

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 p. 1269). 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.