RT Journal Article
SR Electronic
T1 An Arf6- and caveolae-dependent pathway links hemidesmosome remodeling and mechanoresponse
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 126151
DO 10.1101/126151
A1 Naël Osmani
A1 Julien Pontabry
A1 Jordi Comelles
A1 Nina Fekonja
A1 Jacky G. Goetz
A1 Daniel Riveline
A1 Elisabeth Georges-Labouesse
A1 Michel Labouesse
YR 2017
UL http://biorxiv.org/content/early/2017/04/10/126151.abstract
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.