2. Academic Validation
  3. SPACA9 is a lumenal protein of human ciliary singlet and doublet microtubules

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

  • Proc Natl Acad Sci U S A. 2022 Oct 11;119(41):e2207605119. doi: 10.1073/pnas.2207605119.
Miao Gui 1,  Jacob T Croft 2 3,  Davide Zabeo 2,  Vajradhar Acharya 2,  Justin M Kollman 3,  Thomas Burgoyne 4 5,  Johanna L Höög 2,  Alan Brown 1
Affiliations

Affiliations

  • 1 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
  • 2 Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg 41390, Sweden.
  • 3 Department of Biochemistry, University of Washington, Seattle, WA 98195.
  • 4 Royal Brompton Hospital, Guy's and St Thomas' NHS Foundation Trust, London SW3 6NP, United Kingdom.
  • 5 Institute of Ophthalmology, University College London, London EC1V 9EL, United Kingdom.
PMID: 36191189 DOI: 10.1073/pnas.2207605119
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.

Keywords

axoneme; cilia; cryo-EM; cryo-ET; microtubules.

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