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 Ca2+ concentration ([Ca2+](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 Ca2+. In the present study, the behavior of adenomatous polyposis coli (APC) following an increase in [Ca2+](i) was observed using Xenopus A6 epithelial cell expressing GFP-tagged APC. An increase in [Ca2+](i) by cell membrane disruption or by ionomycin treatment induced dissociation of APC without depolymerizing MTs. Inhibition of a tyrosine kinase and GSK-3 beta suppressed APC dissociation upon an increase in [Ca2+](i). Western blotting analysis showed that Ca2+ transients activated GSK-3 beta through a tyrosine kinase. These results suggest that Ca2+ stimulates redistribution of APC through a tyrosine kinase-and GSK-3 beta-dependent pathway. (C) 2009 Elsevier Inc. All rights reserved.