| First Author | Mathew S | Year | 2012 |
| Journal | Mol Cell Biol | Volume | 32 |
| Issue | 20 | Pages | 4080-91 |
| PubMed ID | 22869523 | Mgi Jnum | J:189261 |
| Mgi Id | MGI:5444810 | Doi | 10.1128/MCB.00568-12 |
| Citation | Mathew S, et al. (2012) beta1 integrin NPXY motifs regulate kidney collecting-duct development and maintenance by induced-fit interactions with cytosolic proteins. Mol Cell Biol 32(20):4080-91 |
| abstractText | Loss of beta1 integrin expression inhibits renal collecting-system development. Two highly conserved NPXY motifs in the distal beta1 tail regulate integrin function by associating with phosphtyrosine binding (PTB) proteins, such as talin and kindlin. Here, we define the roles of these two tyrosines in collecting-system development and delineate the structural determinants of the distal beta1 tail using nuclear magnetic resonance (NMR). Mice carrying alanine mutations have moderate renal collecting-system developmental abnormalities relative to beta1-null mice. Phenylalanine mutations did not affect renal collecting-system development but increased susceptibility to renal injury. NMR spectra in bicelles showed the distal beta1 tail is disordered and does not interact with the model membrane surface. Alanine or phenylalanine mutations did not alter beta1 structure or interactions between alpha and beta1 subunit transmembrane/cytoplasmic domains; however, they did decrease talin and kindlin binding. Thus, these studies highlight the fact that the functional roles of the NPXY motifs are organ dependent. Moreover, the beta1 cytoplasmic tail, in the context of the adjacent transmembrane domain in bicelles, is significantly different from the more ordered, membrane-associated beta3 integrin tail. Finally, tyrosine mutations of beta1 NPXY motifs induce phenotypes by disrupting their interactions with critical integrin binding proteins like talins and kindlins. |
