PT - JOURNAL ARTICLE AU - Naël Osmani AU - Julien Pontabry AU - Jordi Comelles AU - Nina Fekonja AU - Jacky G. Goetz AU - Daniel Riveline AU - Elisabeth Georges-Labouesse AU - Michel Labouesse TI - An Arf6- and caveolae-dependent pathway links hemidesmosome remodeling and mechanoresponse AID - 10.1101/126151 DP - 2017 Jan 01 TA - bioRxiv PG - 126151 4099 - http://biorxiv.org/content/early/2017/04/10/126151.short 4100 - http://biorxiv.org/content/early/2017/04/10/126151.full AB - Hemidesmosomes (HDs) are epithelial-specific cell-matrix adhesions, which stably anchor the intracellular keratin network to the extracellular matrix. Although their main role is to protect the epithelial sheet from external mechanical strain, how HDs respond to mechanical stress remains poorly understood. Here we identify a pathway essential for HD remodeling, and outline its role with respect to α6β4 integrin recycling. We find that α6β4 integrin chains localize to the plasma membrane/caveolae and Arf6+ endocytic compartments. Based on FRAP and endocytosis assays, integrin recycling between both sites requires the small GTPase Arf6 and its co-regulators GIT1/βPIX, but neither Caveolin1 (Cav1) nor Cavin1. Strikingly, when keratinocytes are stretched or hypo-osmotically shocked, α6β4 integrin accumulates at cell edges, whereas Cav1 disappears from it. This process, which is isotropic relative to the orientation of stretch, depends on Arf6, Cav1 and Cavin1. We propose that mechanically-induced HD growth involves the isotropic flattening of caveolae (known for their mechanical buffering role) associated with integrin diffusion and turnover.