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Microtubule-bundling protein Spef1 enables mammalian ciliary central apparatus formation Free
Jianqun Zheng 1,2,† , Hao Liu 1,2,† , Lei Zhu 1,2 , Yawen Chen 1,2 , Huijie Zhao 1 , Wei Zhang 1 , Fan Li 1,2 , Lele Xie 1 , Xiumin Yan 1,* , and Xueliang Zhu 1,2,*
1 State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China
2 University of Chinese Academy of Sciences, Shanghai 200031, China
These authors contributed equally to this work.
*Correspondence to:Xueliang Zhu, E-mail: xlzhu@sibcb.ac.cn; Xiumin Yan, E-mail: yanx@sibcb.ac.cn
J Mol Cell Biol, Volume 11, Issue 1, January 2019, 67-77,  https://doi.org/10.1093/jmcb/mjy014
Keyword: central pair apparatus, cilium, microtubule, mouse ependymal cell, mouse tracheal epithelial cell, Spef1

Cilia are cellular protrusions containing nine microtubule (MT) doublets and function to propel cell movement or extracellular liquid flow through beating or sense environmental stimuli through signal transductions. Cilia require the central pair (CP) apparatus, consisting of two CP MTs covered with projections of CP proteins, for planar strokes. How the CP MTs of such ‘9 + 2’ cilia are constructed, however, remains unknown. Here we identify Spef1, an evolutionarily conserved microtubule-bundling protein, as a core CP MT regulator in mammalian cilia. Spef1 was selectively expressed in mammalian cells with 9 + 2 cilia and specifically localized along the CP. Its depletion in multiciliated mouse ependymal cells by RNAi completely abolished the CP MTs and markedly attenuated ciliary localizations of CP proteins such as Hydin and Spag6, resulting in rotational beat of the ependymal cilia. Spef1, which binds to MTs through its N-terminal calponin-homologous domain, formed homodimers through its C-terminal coiled coil region to bundle and stabilize MTs. Disruption of either the MT-binding or the dimerization activity abolished the ability of exogenous Spef1 to restore the structure and functions of the CP apparatus. We propose that Spef1 bundles and stabilizes central MTs to enable the assembly and functions of the CP apparatus.