Journal Article

Scrib regulates PAK activity during the cell migration process

Sébastien Nola, Michael Sebbagh, Sylvie Marchetto, Naël Osmani, Claire Nourry, Stéphane Audebert, Christel Navarro, Rivka Rachel, Mireille Montcouquiol, Nathalie Sans, Sandrine Etienne-Manneville, Jean-Paul Borg and Marie-Josée Santoni

in Human Molecular Genetics

Volume 17, issue 22, pages 3552-3565
Published in print November 2008 | ISSN: 0964-6906
Published online August 2008 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddn248
Scrib regulates PAK activity during the cell migration process

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Genetic studies have highlighted the key role of Scrib in the development of Metazoans. Deficiency in Scrib impairs many aspects of cell polarity and cell movement although the mechanisms involved remain unclear. In mammals, Scrib belongs to a protein complex containing βPIX, an exchange factor for Rac/Cdc42, and GIT1, a GTPase activating protein for ARF6 implicated in receptor recycling and exocytosis. Here we show that the Scrib complex associates with PAK, a serine–threonine kinase family crucial for cell migration. PAK colocalizes with members of the Scrib complex at the leading edge of heregulin-treated T47D breast cancer cells. We demonstrate that the Scrib complex is required for epithelial cells and primary mouse embryonic fibroblasts to efficiently respond to chemoattractant cues. In Scrib-deficient cells, the pool of cortical PAK is decreased, thereby precluding its proper activation by Rac. Loss of Scrib also impairs the polarized distribution of active Rac at the leading edge and compromises the regulated activation of the GTPase in T47D cells and mouse embryonic fibroblasts. These data underscore the role of Scrib in cell migration and show the strong impact of Scrib in the function of PAK and Rac, two key molecules implicated in this process.

Journal Article.  8666 words.  Illustrated.

Subjects: Genetics and Genomics

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