Research ArticleCell Biology

FAM123A Binds to Microtubules and Inhibits the Guanine Nucleotide Exchange Factor ARHGEF2 to Decrease Actomyosin Contractility

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Sci. Signal.  04 Sep 2012:
Vol. 5, Issue 240, pp. ra64
DOI: 10.1126/scisignal.2002871

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The Microtubule Regulator in the Family

Mutations in the tumor suppressor WTX, which is also known as FAM123B, are associated with Wilms disease in children. To better define the cellular functions of the other members of the FAM123 family, Siesser et al. characterized the protein-protein interaction networks for FAM123A, WTX, and FAM123C and found that in contrast to the other FAM123 family members, FAM123A interacted with microtubule-associated proteins. Biochemical, cellular, and imaging assays indicated that FAM123A altered microtubule dynamics and limited actomyosin contractility, a property that generates the mechanical force required for changes in cell shape, which in turn can regulate cell adhesion and migration. Indeed, cells lacking FAM123A showed increased adhesion and decreased migration.