The Rac activator STEF (Tiam2) regulates cell migration by microtubule-mediated focal adhesion disassembly.
AuthorsRooney, Claire M
White, Gavin R M
Woodcock, Simon A
Anderson, Kurt I
AffiliationCell Signalling Group, Cancer Research UK Paterson Institute for Cancer Research, The University of Manchester, Manchester M20 4BX, UK.
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AbstractFocal adhesion (FA) disassembly required for optimal cell migration is mediated by microtubules (MTs); targeting of FAs by MTs coincides with their disassembly. Regrowth of MTs, induced by removal of the MT destabilizer nocodazole, activates the Rho-like GTPase Rac, concomitant with FA disassembly. Here, we show that the Rac guanine nucleotide exchange factor (GEF) Sif and Tiam1-like exchange factor (STEF) is responsible for Rac activation during MT regrowth. Importantly, STEF is required for multiple targeting of FAs by MTs. As a result, FAs in STEF-knockdown cells have a reduced disassembly rate and are consequently enlarged. This leads to reduced speed of migration. Together, these findings suggest a new role for STEF in FA disassembly and cell migration through MT-mediated mechanisms.
CitationThe Rac activator STEF (Tiam2) regulates cell migration by microtubule-mediated focal adhesion disassembly. 2010, 11 (4):292-8 EMBO Rep
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