| First Author | Zhu T | Year | 2013 |
| Journal | J Biol Chem | Volume | 288 |
| Issue | 8 | Pages | 5268-77 |
| PubMed ID | 23300084 | Mgi Jnum | J:196716 |
| Mgi Id | MGI:5489055 | Doi | 10.1074/jbc.M112.446054 |
| Citation | Zhu T, et al. (2013) Type I phosphotidylinosotol 4-phosphate 5-kinase gamma regulates osteoclasts in a bifunctional manner. J Biol Chem 288(8):5268-77 |
| abstractText | Type 1 phosphotidylinosotol-4 phosphate 5 kinase gamma (PIP5KIgamma) is central to generation of phosphotidylinosotol (4,5)P(2) (PI(4,5)P(2)). PIP5KIgamma also participates in cytoskeletal organization by delivering talin to integrins, thereby enhancing their ligand binding capacity. As the cytoskeleton is pivotal to osteoclast function, we hypothesized that absence of PIP5KIgamma would compromise their resorptive capacity. Absence of the kinase diminishes PI(4,5) abundance and desensitizes precursors to RANK ligand-stimulated differentiation. Thus, PIP5KIgamma(-/-) osteoclasts are reduced in number in vitro and confirm physiological relevance in vivo. Despite reduced numbers, PIP5KIgamma(-/-) osteoclasts surprisingly have normal cytoskeletons and effectively resorb bone. PIP5KIgamma overexpression, which increases PI(4,5)P(2), also delays osteoclast differentiation and reduces cell number but in contrast to cells lacking the kinase, its excess disrupts the cytoskeleton. The cytoskeleton-disruptive effects of excess PIP5KIgamma reflect its kinase activity and are independent of talin recognition. The combined arrested differentiation and disorganized cytoskeleton of PIP5KIgamma-transduced osteoclasts compromises bone resorption. Thus, optimal PIP5KIgamma and PI(4,5)P(2) expression, by osteoclasts, are essential for skeletal homeostasis. |
