An Arf6- and caveolae-dependent pathway links hemidesmosome remodeling and mechanoresponse.
Mol Biol Cell
; 29(4): 435-451, 2018 02 15.
Article
in En
| MEDLINE
| ID: mdl-29237817
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 α6ß4 integrin recycling. We find that α6ß4 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, α6ß4 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.
Full text:
1
Database:
MEDLINE
Main subject:
Keratinocytes
/
ADP-Ribosylation Factors
/
Hemidesmosomes
/
Integrin beta4
/
Caveolin 1
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Year:
2018
Type:
Article