Ca(2+) regulates the subcellular localization of adenomatous polyposis coli tumor suppressor protein.

Microtubule (MT) plus-end tracking proteins (+TIPs) are involved in the regulation of MT plus-end dynamics and stabilization. It was reported previously that an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) induced by disruption of the plasma membrane stimulates rearrangement of MTs [T. Togo, Disruption of the plasma membrane stimulates rearrangement of microtubules and lipid traffic toward the wound site, J. Cell Sci. 119 (2006) 2780-2786], suggesting that some +TIPs are regulated by Ca(2+). In the present study, the behavior of adenomatous polyposis coli (APC) following an increase in [Ca(2+)](i) was observed using Xenopus A6 epithelial cell expressing GFP-tagged APC. An increase in [Ca(2+)](i) by cell membrane disruption or by ionomycin treatment induced dissociation of APC without depolymerizing MTs. Inhibition of a tyrosine kinase and GSK-3beta suppressed APC dissociation upon an increase in [Ca(2+)](i). Western blotting analysis showed that Ca(2+) transients activated GSK-3beta through a tyrosine kinase. These results suggest that Ca(2+) stimulates redistribution of APC through a tyrosine kinase- and GSK-3beta-dependent pathway.