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© Pierre Gounon
Entrée de Listeria dans une cellule épithéliale (Grossissement X 10000). Image colorisée.
Publication : Nature cell biology

ARHGAP10 is necessary for alpha-catenin recruitment at adherens junctions and for Listeria invasion

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Nature cell biology - 25 Sep 2005

Sousa S, Cabanes D, Archambaud C, Colland F, Lemichez E, Popoff M, Boisson-Dupuis S, Gouin E, Lecuit M, Legrain P, Cossart P

Link to Pubmed [PMID] – 16184169

Nat. Cell Biol. 2005 Oct;7(10):954-60

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.

http://www.ncbi.nlm.nih.gov/pubmed/16184169