Arg Links Actin and Microtubules

Science's STKE  18 May 2004:
Vol. 2004, Issue 233, pp. tw174-TW174
DOI: 10.1126/stke.2332004TW174

Microtubules and the actin cytoskeleton work together during cell movement. Indeed, microtubule capture sites exist in the cortical actin network. Miller et al. show that the Abl-related gene (Arg), which is a protein of the Abl family of nonreceptor tyrosine kinases that regulate cell motility and morphology and which has binding sites for both actin and microtubules, serves to link the actin and microtubule cytoskeletons. It was previously determined that in vitro and in vivo, Arg promoted actin bundling. Miller et al. show that Arg-deficient fibroblasts plated on fibronectin do not form lamellipodia and membrane ruffling seen with wild-type cells. Introduction of Arg or an Arg-YFP (green fluorescent protein variant) fusion protein rescued the lamellipodia defect. In vitro, Arg cosedimented with microtubules, and this interaction required a microtubule-binding motif in the C-terminal region. Incubation of Arg with microtubules and filamentous actin (F-actin) resulted in the formation of cross-linked arrays or in cosedimentation of all three components. When expressed in transfected arg–/– cells, Arg-YFP was concentrated in the cell periphery at sites of cell protrusions and promoted the concentration of F-actin and microtubules at such sites. This concentration of Arg required an intact actin cytoskeleton (it was disrupted by latrunculin A) and intact microtubules (it was disrupted by nocodazole). Finally, the C-terminal region containing both the microtubule- and actin-binding sites was required for rescuing the lamellipodial defects in arg–/– cells and for promoting the formation of concentrated regions of Arg, F-actin, and microtubule in cell protrusions. Thus, Arg appears to be one of the proteins that links the actin and microtubule cytoskeletons to allow cells to undergo morphological changes in response to interactions with the extracellular matrix.

A. L. Miller, Y. Wang, M. S. Mooseker, A. J. Koleske, The Able-related gene (Arg) requires its F-actin-microtubule cross-linking activity to regulate lamellipodial dynamics during fibroblast adhesion. J. Cell Biol. 165, 407-419 (2004). [Abstract] [Full Text]