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Sci. STKE, 18 February 2003
Vol. 2003, Issue 170, p. tw76
[DOI: 10.1126/stke.2003.170.tw76]

EDITORS' CHOICE

Cell Migration GSK-3β Connects Microtubule Organization to GTPase Activation

How do cells reorient their microtubules to promote directional movement? That is the question addressed by Etienne-Manneville and Hall. They found that activation of the small guanosine triphosphatase (GTPase) Cdc42, which is known to interact with an atypical protein kinase C complex, during scratch-induced cell migration of astrocytes resulted in the phosphorylation of glycogen synthase kinase 3β (GSK-3β) at the leading edge of the migrating cells. Injection of constitutively activated or kinase-dead GSK-3β into the leading edge of the cells inhibited reorientation of the centrosome, which directs microtubule polymerization, and induction of cell polarity. Instead the cells formed randomly appearing protrusions that were not oriented toward the scratch. Phosphorylation of GSK-3β inhibits its kinase activity. One of the substrates of GSK-3β is the tumor suppressor adenomatous polyposis coli (APC), which can interact with microtubules. APC associated with the plus end of microtubules at the leading edge of the migrating cells. Thus, localized inhibition of GSK-3β appears to contribute to the recruitment of APC, which is important for the organized polymerization of microtubules to allow polarized cell migration.

S. Etienne-Manneville, A. Hall, Cdc42 regulates GSK-3β and adenomatous polyposis coli to control cell polarity. Nature 421, 753-756 (2003). [Online Journal]

Citation: GSK-3β Connects Microtubule Organization to GTPase Activation. Sci. STKE 2003, tw76 (2003).


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