SPACA9 is a lumenal protein of human ciliary singlet and doublet microtubules


Miao Gui, Jacob T. Croft, Davide Zabeo, Vajradhar Acharya, Justin M. Kollman, Thomas Burgoyne, Johanna L. Höög, and Alan Brown. 10/3/2022. “SPACA9 is a lumenal protein of human ciliary singlet and doublet microtubules.” Proceedings of the National Academy of Sciences, 119, 41, Pp. e2207605119. Publisher's Version


The cilium-centrosome complex contains triplet, doublet, and singlet microtubules. The lumenal surfaces of each microtubule within this diverse array are decorated by microtubule inner proteins (MIPs). Here, we used single-particle cryo-electron microscopy methods to build atomic models of two types of human ciliary microtubule: the doublet microtubules of multiciliated respiratory cells and the distal singlet microtubules of monoflagellated human spermatozoa. We discover that SPACA9 is a polyspecific MIP capable of binding both microtubule types. SPACA9 forms intralumenal striations in the B tubule of respiratory doublet microtubules and noncontinuous spirals in sperm singlet microtubules. By acquiring new and reanalyzing previous cryo-electron tomography data, we show that SPACA9-like intralumenal striations are common features of different microtubule types in animal cilia. Our structures provide detailed references to help rationalize ciliopathy-causing mutations and position cryo-EM as a tool for the analysis of samples obtained directly from ciliopathy patients.
Last updated on 10/05/2022