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The Rac activator STEF (Tiam2) regulates cell migration by microtubule-mediated focal adhesion disassembly.

ABSTRACT: Focal 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.

SUBMITTER: Rooney C

PROVIDER: S-EPMC2854589 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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The Rac activator STEF (Tiam2) regulates cell migration by microtubule-mediated focal adhesion disassembly.

Rooney Claire C White Gavin G Nazgiewicz Alicja A Woodcock Simon A SA Anderson Kurt I KI Ballestrem Christoph C Malliri Angeliki A

EMBO reports 20100312 4

Focal 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 mu ...[more]

PMID: 20224579

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