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PMID:21368832

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Citation

Zhang, H, Landmann, F, Zahreddine, H, Rodriguez, D, Koch, M and Labouesse, M (2011) A tension-induced mechanotransduction pathway promotes epithelial morphogenesis. Nature 471:99-103

Abstract

Mechanotransduction refers to the transformation of physical forces into chemical signals. It generally involves stretch-sensitive channels or conformational change of cytoskeleton-associated proteins. Mechanotransduction is crucial for the physiology of several organs and for cell migration. The extent to which mechanical inputs contribute to development, and how they do this, remains poorly defined. Here we show that a mechanotransduction pathway operates between the body-wall muscles of Caenorhabditis elegans and the epidermis. This pathway involves, in addition to a Rac GTPase, three signalling proteins found at the hemidesmosome: p21-activated kinase (PAK-1), the adaptor GIT-1 and its partner PIX-1. The phosphorylation of intermediate filaments is one output of this pathway. Tension exerted by adjacent muscles or externally exerted mechanical pressure maintains GIT-1 at hemidesmosomes and stimulates PAK-1 activity through PIX-1 and Rac. This pathway promotes the maturation of a hemidesmosome into a junction that can resist mechanical stress and contributes to coordinating the morphogenesis of epidermal and muscle tissues. Our findings suggest that the C. elegans hemidesmosome is not only an attachment structure, but also a mechanosensor that responds to tension by triggering signalling processes. We suggest that similar pathways could promote epithelial morphogenesis or wound healing in other organisms in which epithelial cells adhere to tension-generating contractile cells.

Links

PubMed Online version:10.1038/nature09765

Keywords

Animals; Caenorhabditis elegans/cytology; Caenorhabditis elegans/embryology; Caenorhabditis elegans/enzymology; Caenorhabditis elegans/metabolism; Caenorhabditis elegans Proteins/metabolism; Carrier Proteins/metabolism; Epidermis/cytology; Epidermis/embryology; Hemidesmosomes/metabolism; Intermediate Filaments/metabolism; Mechanotransduction, Cellular/physiology; Morphogenesis; Muscle Contraction/physiology; Muscles/embryology; Muscles/physiology; Phenotype; Phosphorylation; Signal Transduction; p21-Activated Kinases/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:E3W735

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:G5ECG8

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:G5ECP9

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:G5EDD3

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:G5EEC4

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:G5EFD1

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:G5EFK7

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:G5EFM4

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:G5EFW2

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:H2L0C1

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:PK1

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:Q19467

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:Q21430

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:Q9BKP3

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:Q9UB28

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:Q9UB29

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

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