E-cadherin mediates the formation of
adherens junctions between
epithelial cells. It serves as a receptor for
Listeria monocytogenes, a
bacterial pathogen that enters
epithelial cells. The
L. monocytogenes surface protein, InlA, interacts with the
extracellular domain of
E-cadherin. In
adherens junctions, this ectodomain is involved in homophilic interactions whereas the
cytoplasmic domain binds
beta-catenin, which then recruits
alpha-catenin.
alpha-catenin binds to
actin directly, or indirectly, thus linking
E-cadherin to the
actin cytoskeleton. Entry of
L. monocytogenes into cells and
adherens junction formation are dynamic events that involve
actin and membrane
rearrangements. To understand these processes better, we searched for new ligands of
alpha-catenin. Using a
two-hybrid screen, we identified a new partner of
alpha-catenin: ARHGAP10. This protein colocalized with
alpha-catenin at cell-cell junctions and was recruited at
L. monocytogenes entry sites. In ARHGAP10-knockdown cells,
L. monocytogenes entry and
alpha-catenin recruitment at cell-cell contacts were
impaired. The GAP domain of ARHGAP10 has GAP activity for
RhoA and
Cdc42. Its
overexpression disrupted
actin cables, enhanced
alpha-catenin and cortical
actin levels at cell-cell junctions and inhibited
L. monocytogenes entry. Altogether, our results show that ARHGAP10 is a new component of cell-cell junctions that controls
alpha-catenin recruitment and has a key role during
L. monocytogenes uptake.
