Temporal and spatial remodelling of the actin cytoskeleton is important for cell morphology and migration. The mammalian homologue of Diaphanous (mDia) – an actin nucleator that forms unbranched actin filaments – is an effector of the small GTPase RhoA, which itself is a key regulator of actin remodelling. But how is mDia activity regulated in cells? To answer this question, Shuh Narumiya and colleagues (p. ) have been looking for mDia-binding proteins in mouse brain lysates using an N-terminal mDia1 fragment as bait. mDia is autoregulated through an intra-molecular interaction between an N-terminal Dia-inhibitory domain (DID) and a C-terminal Dia autoregulatory domain (DAD). Binding of GTP-bound RhoA to mDia disrupts this intra-molecular interaction and activates mDia. In their pull-down assay, the authors identify Liprin-α (an interacting protein of the leukocyte common antigen-related family of receptor protein tyrosine phosphatases) as an mDia-binding protein. Liprin-α, they report, binds to the active form of mDia through the DID and negatively regulates the localization of mDia to the plasma membrane and the formation of actin stress fibres. Thus, they conclude, Liprin-α is a negative regulator of mDia, and further studies on this function of Liprin-α could shed new light onto the regulation of mDia-mediated actin remodelling in cells. (written by Jane Bradbury)
