NME7 maintains primary cilium assembly, ciliary microtubule stability, and Hedgehog signaling

Abstract

NME7 (nucleoside diphosphate kinase 7), a lesser studied member of the non-metastatic expressed (NME) family, has been reported as a potential subunit of the γ-tubulin ring complex (γTuRC). However, its role in the cilium assembly and function remains unclear. Our research demonstrated that NME7 is located at the centrosome, including at the spindle poles during metaphase and at the basal bodies during cilium assembly. Notably, a small fraction of NME7 localizes within the cilium. Detailed analysis of cilium assembly after NME7 knockdown and knockout revealed that NME7 is required for this process. NME7 knockout cells exhibited sensitivity to nocodazole, indicating its role in ciliary microtubule stability. In addition, NME7 deficiency impacted the Hedgehog signaling pathway, evident from reduced smoothened (Smo) fluorescence within primary cilia. This role of NME7 in Hedgehog signaling may depend on its nucleoside diphosphate kinase activity and γTuRC association. In conclusion, these findings enhance our understanding of the γTuRC roles in primary cilia in mammalian cells, highlighting the importance of NME7 in ciliary functions and signaling pathways.