The formin homology protein mDia is a Rho GTPase effector protein that participates in stress fiber formation, cytokinesis, and transcriptional activation of the serum response factor. Although the function of another effector of Rho, Rho-associated kinase, is well established, relatively little is known about the functional mechanism and the downstream targets of mDia. Our recent report of a Rho-mDia-Src-tyrosine kinase pathway suggested an important role for mDia in cell adhesion turnover. We identified a new mDia-interacting protein which is expressed ubiquitously. The new protein mainly binds to the proline-rich region of mDia through its Src homology 3 domain and also binds to Grb2 through its proline-rich domain. The protein is localized at the cell periphery and membrane ruffles and co-localizes with mDia. Co-expression of vSrc and the mDia-interacting protein induces significant morphological changes at focal contacts and activation of vSrc. Furthermore, we found that the mDia-interacting protein plays an important role in stress fiber formation induced by active mDia1. Our results suggest that this new protein regulates actin polymerization and cell adhesion turnover in the downstream portion of the RhomDia pathway by interacting with Grb2 and Src.

These results indicate that taxilin is a novel binding partner of several syntaxin family members and suggest that taxilin is involved in Ca2+-dependent exocytosis in neuroendocrine cells.

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α α α α -Taxilin is a novel binding partner of the syntaxin family, which is implicated in intracellular vesicle traffic. We have here found that α α α α -taxilin interacts with the nascent polypeptide-associated complex (NAC), which is involved in transferring growing nascent polypeptide chains to appropriate co-translationally acting factors. NAC is composed of two subunits, α α α α -and β β β β NACs. Both these subunits bound to α α α α -taxilin through its C-terminal coiled-coil region in dose-dependent and saturable manners. The interactions of α α α α -taxilin with α α α α NAC and NAC but not with β β β β NAC were inhibited by syntaxin-4, indicating that α α α α -taxilin binds to NAC mainly through its interaction with α α α α NAC. When α α α α NAC was over-expressed in COS-7 cells, α α α α NAC was distributed in the cytosol and nucleus. However, co-expression of the α α α α -taxilin fragment containing the α α α α NAC-binding region eliminated the nuclear distribution of over-expressed α α α α NAC. Moreover, other taxilin family members, β β β β -and γ γ γ γ -taxilins, also bound to α α α α NAC and thereby affected the nuclear distribution of overexpressed α α α α NAC. Taken together with the evidence that α α α α NAC functions in the nucleus as a transcriptional coactivator, our results raise the possibility that the taxilin family is involved not only in the translational process through its interaction with NAC but also in the transcriptional process through its interaction with α α α α NAC alone.

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