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

Gui, Miao; Croft, Jacob T; Zabeo, Davide; Acharya, Vajradhar; Kollman, Justin M; Burgoyne, Thomas; Höög, Johanna L; (2022) SPACA9 is a lumenal protein of human ciliary singlet and doublet microtubules. Proceedings of the National Academy of Sciences , 119 (41) , Article e2207605119. 10.1073/pnas.2207605119. Green open access

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Abstract

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.

Type: Article
Title: SPACA9 is a lumenal protein of human ciliary singlet and doublet microtubules
Open access status: An open access version is available from UCL Discovery
DOI: 10.1073/pnas.2207605119
Publisher version: https://doi.org/10.1073/pnas.2207605119
Language: English
Additional information: Copyright © 2022 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10156726
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