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Mol Biol Cell. 2018 Feb 15;29(4):435-451. doi: 10.1091/mbc.E17-06-0356. Epub 2017 Dec 13.

An Arf6- and caveolae-dependent pathway links hemidesmosome remodeling and mechanoresponse.

Osmani N1,2,3,4,5, Pontabry J1,3, Comelles J1,3,6, Fekonja N2,3,4,5, Goetz JG2,3,4,5, Riveline D7,3,6, Georges-Labouesse E1,3, Labouesse M7,3,8.

Author information

1
IGBMC, Development and Stem Cells Program, CNRS (UMR 7104)/INSERM (U964), 67400 Illkirch, France.
2
Inserm U1109, MN3T, 67200 Strasbourg, France.
3
Université de Strasbourg, 67000 Strasbourg, France.
4
LabEx Medalis, Université de Strasbourg, Strasbourg 67000, France.
5
Fédération de Médecine Translationnelle de Strasbourg (FMTS), 67000 Strasbourg, France.
6
Laboratory of Cell Physics, ISIS/IGBMC, CNRS UMR 7006, 67000 Strasbourg, France.
7
IGBMC, Development and Stem Cells Program, CNRS (UMR 7104)/INSERM (U964), 67400 Illkirch, France michel.labouesse@upmc.fr riveline@unistra.fr.
8
UMR7622-CNRS, IBPS, Sorbonne Université, 75005 Paris, France.

Abstract

Hemidesmosomes (HDs) are epithelial-specific cell-matrix adhesions that 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 ADP-ribosylation factor-6+ (Arf6+) endocytic compartments. Based on fluorescence recovery after photobleaching and endocytosis assays, integrin recycling between both sites requires the small GTPase Arf6 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.

PMID:
29237817
PMCID:
PMC6014169
DOI:
10.1091/mbc.E17-06-0356
[Indexed for MEDLINE]
Free PMC Article

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