Microtubule-dependent redistribution of the type-1 inositol 1,4,5-trisphosphate receptor in A7r5 smooth muscle cells Available to Purchase

In A7r5 vascular smooth muscle cells, the two expressed inositol 1,4,5-trisphosphate receptor (IP₃R) isoforms were differentially localized. IP₃R1 was predominantly localized in the perinuclear region, whereas IP₃R3 was homogeneously distributed over the cytoplasm. Prolonged stimulation (1-5 hours) of cells with 3 μM argininevasopressin induced a redistribution of IP₃R1 from the perinuclear region to the entire cytoplasm, whereas the localization of IP₃R3 appeared to be unaffected. The redistribution process occurred independently of IP₃R downregulation. No structural changes of the endoplasmic reticulum were observed, but SERCA-type Ca²⁺ pumps redistributed similarly to IP₃R1. The change in IP₃R1 localization induced by arginine-vasopressin could be blocked by the simultaneous addition of nocodazole or taxol and depended on Ca²⁺ release from intracellular stores since Ca²⁺-mobilizing agents such as thapsigargin and cyclopiazonic acid could induce the redistribution. Furthermore, various protein kinase C inhibitors could inhibit the redistribution of IP₃R1, whereas the protein kinase C activator 1-oleoyl-2-acetyl-sn-glycerol induced the redistribution. Activation of protein kinase C also induced an outgrowth of the microtubules from the perinuclear region into the cytoplasm, similar to what was seen for the redistribution of IP₃R1. Finally, blocking vesicular transport at the level of the intermediate compartment inhibited the redistribution. Taken together, these findings suggest a role for protein kinase C and microtubuli in the redistribution of IP₃R1, which probably occurs via a mechanism of vesicular trafficking.