| First Author | Yazlovitskaya EM | Year | 2019 |
| Journal | Matrix Biol | Volume | 77 |
| Pages | 101-116 | PubMed ID | 30193894 |
| Mgi Jnum | J:275664 | Mgi Id | MGI:6313535 |
| Doi | 10.1016/j.matbio.2018.08.010 | Citation | Yazlovitskaya EM, et al. (2019) The laminin binding alpha3 and alpha6 integrins cooperate to promote epithelial cell adhesion and growth. Matrix Biol 77:101-116 |
| abstractText | 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 alpha3beta1, alpha6beta1 and alpha6beta4 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 alpha3 and alpha6 integrin subunits. This deletion impaired cell adhesion and migration to LM-332 and LM-511 more than deleting alpha3 or alpha6 alone. Cell adhesion mediated by both alpha3beta1 and alpha6 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 alpha3/alpha6- but not single alpha3- or alpha6-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 alpha3 or alpha6 subunit is sufficient to mediate GDNF- and FGF10-dependent spreading, proliferation and signaling on LM-511. Thus, our study shows that alpha3 and alpha6 containing integrins promote distinct functions and signaling by CD cells on laminin substrata. |
