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JCS ePress online publication date 12 Feb 2003
doi: 10.1242/jcs.00354

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Research Article

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


Elke Vermassen, Kristel Van Acker, Wim G. Annaert, Bernard Himpens, Geert Callewaert, Ludwig Missiaen, Humbert De Smedt, and Jan B. Parys*
* Author for correspondence (e-mail: Jan.Parys{at}med.kuleuven.ac.be)

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 arginine-vasopressin 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.


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