Neuronal migration is mediated by inositol hexakisphosphate kinase 1 via α-actinin and focal adhesion kinase.
| Publication Type | Academic Article |
| Authors | Fu C, Xu J, Cheng W, Rojas T, Chin A, Snowman A, Harraz M, Snyder S |
| Journal | Proc Natl Acad Sci U S A |
| Volume | 114 |
| Issue | 8 |
| Pagination | 2036-2041 |
| Date Published | 02/02/2017 |
| ISSN | 1091-6490 |
| Keywords | Actinin, Cell Movement, Focal Adhesion Kinase 1, Neurons, Phosphotransferases (Phosphate Group Acceptor) |
| Abstract | 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 α-actinin and localizes to focal adhesions. IP6K1 deletion disrupts α-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 α-actinin by IP6K1 requires its kinase activity. Deletion of IP6K1 abolishes α-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 α-actinin and influencing phosphorylation of both FAK and α-actinin through its product 5-IP7. |
| DOI | 10.1073/pnas.1700165114 |
| PubMed ID | 28154132 |
| PubMed Central ID | PMC5338408 |