NME7 is a functional component of the γ-tubulin ring complex

As the primary microtubule nucleator in animal cells, the gamma-tubulin ring complex (gamma TuRC) plays a crucial role in microtubule organization, but little is known about how the activity of the gamma TuRC is regulated. Recently, isolated gamma TuRC was found to contain NME7, a poorly characterized member of the NME family. Here we report that NME7 is a gamma TuRC component that regulates the microtubule-nucleating activity of the gamma TuRC. NME7 contains two putative kinase domains, A and B, and shows autophosphorylating activity. Whereas domain A is involved in the autophosphorylation, domain B is inactive. NME7 interacts with the gamma TuRC through both A and B domains, with Arg-322 in domain B being crucial to the binding. In association with the gamma TuRC, NME7 localizes to centrosomes throughout the cell cycle and to mitotic spindles during mitosis. Suppression of NME7 expression does not affect gamma TuRC assembly or localization to centrosomes, but it does impair centrosome-based microtubule nucleation. Of importance, wild-type NME7 promotes gamma TuRC-dependent nucleation of microtubules, but kinase-deficient NME7 does so only poorly. These results suggest that NME7 functions in the gamma TuRC in a kinase-dependent manner to facilitate microtubule nucleation.