Arg Kinase Binding Protein 2 (ArgBP2) interaction with {alpha}-actinin and actin stress fibres inhibits cell migration. [Cell Biology]

November 26th, 2014 by Anekal, P. V., Yong, J., Manser, E.

Cell migration requires dynamic remodelling of the actomyosin network. We report here that an adapter protein, ArgBP2 is a component of α-actinin containing stress fibres and inhibits migration. ArgBP2 is undetectable in many commonly studied cancer derived cell lines. COS-7 and HeLa cells express ArgBP2 (by western analysis), but expression was detectable only in ~half the cells by immuno-fluorescence. Short-term clonal analysis demonstrated 0.2- 0.3% of cells switch ArgBP2 expression (on or off) per cell division. ArgBP2 can have a fundamental impact on the actomyosin network: ArgBP2 positive COS-7 cells, for example, are clearly distinguishable by their denser actomyosin (stress fibre) network. ArgBP2γ binding to α-actinin appears to underlie its ability to localize to stress fibres and to decrease cell migration. We map a small α-actinin binding region in ArgBP2 (residues 192-228) that is essential for these effects. Protein kinase A phosphorylation of ArgBP2γ at neighbouring Ser259 and consequent 14-3-3 binding blocks its interaction with α-actinin. ArgBP2 is known to be down-regulated in some aggressively metastatic cancers. Our work provides a biochemical explanation for the antimigratory effect of ArgBP2.