Data from: Evolutionary rate covariation analysis of E-cadherin identifies Raskol as a regulator of cell adhesion and actin dynamics in Drosophila

The adherens junction couples the actin cytoskeletons of neighboring cells
to provide the foundation for multicellular organization. The core of the
adherens junction is the cadherin-catenin complex that arose early in the
evolution of multicellularity to link actin to intercellular adhesions.
Over time, evolutionary pressures have shaped the signaling and mechanical
functions of the adherens junction to meet specific developmental and
physiological demands. Evolutionary rate covariation (ERC) identifies
proteins with correlated fluctuations in evolutionary rate that can
reflect shared selective pressures and functions. Here we use ERC to
identify proteins with evolutionary histories similar to the Drosophila
E-cadherin (DE-cad) ortholog. Core adherens junction components α-catenin
and p120-catenin displayed positive ERC correlations with DE-cad,
indicating that they evolved under similar selective pressures during
evolution between Drosophila species. Further analysis of the DE-cad ERC
profile revealed a collection of proteins not previously associated with
DE-cad function or cadherin-mediated adhesion. We then analyzed the
function of a subset of ERC-identified candidates by RNAi during border
cell (BC) migration and identified novel genes that function to regulate
DE-cad. Among these, we found that the gene CG42684, which encodes a
putative GTPase activating protein (GAP), regulates BC migration and
adhesion. We named CG42684 raskol (“to split” in Russian) and show that it
regulates DE-cad levels and actin protrusions in BCs. We propose that
Raskol functions with DE-cad to restrict Ras/Rho signaling and help guide
BC migration. Our results demonstrate that a coordinated selective
pressure has shaped the adherens junction and this can be leveraged to
identify novel components of the complexes and signaling pathways that
regulate cadherin-mediated adhesion.