| First Author | Fu C | Year | 2017 |
| Journal | Proc Natl Acad Sci U S A | Volume | 114 |
| Issue | 8 | Pages | 2036-2041 |
| PubMed ID | 28154132 | Mgi Jnum | J:318448 |
| Mgi Id | MGI:6859710 | Doi | 10.1073/pnas.1700165114 |
| Citation | Fu C, et al. (2017) Neuronal migration is mediated by inositol hexakisphosphate kinase 1 via alpha-actinin and focal adhesion kinase. Proc Natl Acad Sci U S A 114(8):2036-2041 |
| abstractText | Inositol hexakisphosphate kinase 1 (IP6K1), which generates 5-diphosphoinositol pentakisphosphate (5-IP7), physiologically mediates numerous functions. We report that IP6K1 deletion leads to brain malformation and abnormalities of neuronal migration. IP6K1 physiologically associates with alpha-actinin and localizes to focal adhesions. IP6K1 deletion disrupts alpha-actinin's intracellular localization and function. The IP6K1 deleted cells display substantial decreases of stress fiber formation and impaired cell migration and spreading. Regulation of alpha-actinin by IP6K1 requires its kinase activity. Deletion of IP6K1 abolishes alpha-actinin tyrosine phosphorylation, which is known to be regulated by focal adhesion kinase (FAK). FAK phosphorylation is substantially decreased in IP6K1 deleted cells. 5-IP7, a product of IP6K1, promotes FAK autophosphorylation. Pharmacologic inhibition of IP6K by TNP [N2-(m-Trifluorobenzyl), N6-(p-nitrobenzyl)purine] recapitulates the phenotype of IP6K1 deletion. These findings establish that IP6K1 physiologically regulates neuronal migration by binding to alpha-actinin and influencing phosphorylation of both FAK and alpha-actinin through its product 5-IP7. |
