as cells begin to form associations, Bves is also present at points of cell-cell contact. Interacting proteins Bves interacts with GEFT, a protein that modulates Rho GTPases, Rac1 and Cdc42, which are important for cell motility through modulation of the actin cytoskeleton. Bves also interacts with VAMP3, a SNARE protein important for vesicle fusion. Additionally, Bves has been shown to interact with the tight junction protein, ZO1, although this interaction is most likely via a protein complex, as a direct physical interaction has never been demonstrated. Function Disruption of Bves results in a wide range of cellular and developmental phenotypes. Grossly, cell motility and cell adhesion are impaired. Only recently have the molecular mechanisms underlying the function of Bves been uncovered. Modulation of Rho GTPases Bves has been shown to interact and co-localize with GEFT, a modulator of Rho GTPase signaling cascades. Disruption of Bves results in decreased cell speed and increased cell roundness, which are cell processes modulated by the Rho GTPases, Rac1 and Cdc42. Accordingly, Bves disruption results in decreased active Rac1 and Cdc42. Taken together, these data demonstrate that Bves modulates Rho GTPase signaling cascades through interaction with GEFT to affect cell movement and morphology. Regulation of vesicular transport Bves has been shown to interact with VAMP3, a member of the SNARE complex that facilitates vesicle fusion. VAMP3 is important for recycling of integrins during cell migration and is also necessary for exocytosis of transferrin. Upon Bves disruption, cell rounding is increased, a phenotype indicative of decreased adhesion and disruption of integrin function. Accordingly, Bves disruption results in impaired integrin recycling, phenocopying the result seen with inhibition of VAMP3. Similarly, disruption of either Bves results in impaired transferrin recycling again, mimicking the result seen with disruption of VAMP3. Thus, Bves is important for VAMP3-mediated vesicular transport underlying cell migration and transferrin recycling. Silencing in malignancy Bves is silenced by promoter hypermethylation in malignancy. Bves is underexpressed in colon, lung, and breast cancer. In colon cancer this occurs very early during tumorigenesis, with Bves underexpression first noted in premalignant adenomas. References External links