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The laminin binding ?3 and ?6 integrins cooperate to promote epithelial cell adhesion and growth.


ABSTRACT: Integrins, the major receptors for cell-extracellular matrix (ECM) interactions, regulate multiple cell biological processes including adhesion, migration, proliferation and growth factor-dependent signaling. The principal laminin (LM) binding integrins ?3?1, ?6?1 and ?6?4 are usually co-expressed in cells and bind to multiple laminins with different affinities making it difficult to define their specific function. In this study, we generated kidney epithelial collecting duct (CD) cells that lack both the ?3 and ?6 integrin subunits. This deletion impaired cell adhesion and migration to LM-332 and LM-511 more than deleting ?3 or ?6 alone. Cell adhesion mediated by both ?3?1 and ?6 integrins was PI3K independent, but required K63-linked polyubiquitination of Akt by the ubiquitin-modifying enzyme TRAF6. Moreover, we provide evidence that glial-derived neurotrophic factor (GDNF) and fibroblast growth factor 10 (FGF10)- mediated cell signaling, spreading and proliferation were severely compromised in double integrin ?3/?6- but not single ?3- or ?6-null CD cells. Interestingly, these growth factor-dependent cell functions required both PI3K- and TRAF6-dependent Akt activation. These data suggest that expression of the integrin ?3 or ?6 subunit is sufficient to mediate GDNF- and FGF10-dependent spreading, proliferation and signaling on LM-511. Thus, our study shows that ?3 and ?6 containing integrins promote distinct functions and signaling by CD cells on laminin substrata.

SUBMITTER: Yazlovitskaya EM 

PROVIDER: S-EPMC6399080 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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The laminin binding α3 and α6 integrins cooperate to promote epithelial cell adhesion and growth.

Yazlovitskaya Eugenia M EM   Viquez Olga M OM   Tu Tianxiang T   De Arcangelis Adele A   Georges-Labouesse Elisabeth E   Sonnenberg Arnoud A   Pozzi Ambra A   Zent Roy R  

Matrix biology : journal of the International Society for Matrix Biology 20180904


Integrins, the major receptors for cell-extracellular matrix (ECM) interactions, regulate multiple cell biological processes including adhesion, migration, proliferation and growth factor-dependent signaling. The principal laminin (LM) binding integrins α3β1, α6β1 and α6β4 are usually co-expressed in cells and bind to multiple laminins with different affinities making it difficult to define their specific function. In this study, we generated kidney epithelial collecting duct (CD) cells that lac  ...[more]

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