Proteins That Control the Geometry of Microtubules at the Ends of Cilia

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2018 Sep 16

PMID 30217954

Citations 25

Authors

Panagiota Louka

Krishna Kumar Vasudevan

Mayukh Guha

Ewa Joachimiak

Dorota Wloga

Raphael F-X Tomasi

Charles N Baroud

Pascale Dupuis-Williams

Domenico F Galati

Chad G Pearson

Luke M Rice

James J Moresco

John R Yates 3rd

Yu-Yang Jiang

Karl Lechtreck

William Dentler

Jacek Gaertig

Affiliations

Soon will be listed here.

Abstract

Cilia, essential motile and sensory organelles, have several compartments: the basal body, transition zone, and the middle and distal axoneme segments. The distal segment accommodates key functions, including cilium assembly and sensory activities. While the middle segment contains doublet microtubules (incomplete B-tubules fused to complete A-tubules), the distal segment contains only A-tubule extensions, and its existence requires coordination of microtubule length at the nanometer scale. We show that three conserved proteins, two of which are mutated in the ciliopathy Joubert syndrome, determine the geometry of the distal segment, by controlling the positions of specific microtubule ends. FAP256/CEP104 promotes A-tubule elongation. CHE-12/Crescerin and ARMC9 act as positive and negative regulators of B-tubule length, respectively. We show that defects in the distal segment dimensions are associated with motile and sensory deficiencies of cilia. Our observations suggest that abnormalities in distal segment organization cause a subset of Joubert syndrome cases.

Citing Articles

Molecular organization of the distal tip of vertebrate motile cilia.

Hong J, Lee C, Papoulas O, Pan J, Takagishi M, Manzi N bioRxiv. 2025; .

PMID: 40027778 PMC: 11870508. DOI: 10.1101/2025.02.19.639145.

Tubulin tyrosination/detyrosination regulate the affinity and sorting of intraflagellar transport trains on axonemal microtubule doublets.

Chhatre A, Stepanek L, Nievergelt A, Alvarez Viar G, Diez S, Pigino G Nat Commun. 2025; 16(1):1055.

PMID: 39865093 PMC: 11770126. DOI: 10.1038/s41467-025-56098-0.

A network of interacting ciliary tip proteins with opposing activities imparts slow and processive microtubule growth.

Saunders H, van den Berg C, Hoogebeen R, Schweizer D, Stecker K, Roepman R Nat Struct Mol Biol. 2025; .

PMID: 39856351 DOI: 10.1038/s41594-025-01483-y.

Structure of the ciliary tip central pair reveals the unique role of the microtubule-seam binding protein SPEF1.

Legal T, Joachimiak E, Parra M, Peng W, Tam A, Black C bioRxiv. 2024; .

PMID: 39677611 PMC: 11642885. DOI: 10.1101/2024.12.02.626492.

Deciphering deep-sea chemosynthetic symbiosis by single-nucleus RNA-sequencing.

Wang H, He K, Zhang H, Zhang Q, Cao L, Li J Elife. 2024; 12.

PMID: 39102287 PMC: 11299980. DOI: 10.7554/eLife.88294.

References

Xiong J, Lu Y, Feng J, Yuan D, Tian M, Chang Y . Tetrahymena functional genomics database (TetraFGD): an integrated resource for Tetrahymena functional genomics. Database (Oxford). 2013; 2013:bat008. PMC: 3594985. DOI: 10.1093/database/bat008. View

Omoto C, Gibbons I, Kamiya R, Shingyoji C, Takahashi K, Witman G . Rotation of the central pair microtubules in eukaryotic flagella. Mol Biol Cell. 1999; 10(1):1-4. PMC: 25148. DOI: 10.1091/mbc.10.1.1. View

Goujon M, McWilliam H, Li W, Valentin F, Squizzato S, Paern J . A new bioinformatics analysis tools framework at EMBL-EBI. Nucleic Acids Res. 2010; 38(Web Server issue):W695-9. PMC: 2896090. DOI: 10.1093/nar/gkq313. View

Rezabkova L, Kraatz S, Akhmanova A, Steinmetz M, Kammerer R . Biophysical and Structural Characterization of the Centriolar Protein Cep104 Interaction Network. J Biol Chem. 2016; 291(35):18496-504. PMC: 5000094. DOI: 10.1074/jbc.M116.739771. View

Duan J, Gorovsky M . Both carboxy-terminal tails of alpha- and beta-tubulin are essential, but either one will suffice. Curr Biol. 2002; 12(4):313-6. DOI: 10.1016/s0960-9822(02)00651-6. View

Widlund P, Stear J, Pozniakovsky A, Zanic M, Reber S, Brouhard G . XMAP215 polymerase activity is built by combining multiple tubulin-binding TOG domains and a basic lattice-binding region. Proc Natl Acad Sci U S A. 2011; 108(7):2741-6. PMC: 3041093. DOI: 10.1073/pnas.1016498108. View

Van De Weghe J, Rusterholz T, Latour B, Grout M, Aldinger K, Shaheen R . Mutations in ARMC9, which Encodes a Basal Body Protein, Cause Joubert Syndrome in Humans and Ciliopathy Phenotypes in Zebrafish. Am J Hum Genet. 2017; 101(1):23-36. PMC: 5501774. DOI: 10.1016/j.ajhg.2017.05.010. View

Calzone F, Gorovsky M . Cilia regeneration in Tetrahymena. A simple reproducible method for producing large numbers of regenerating cells. Exp Cell Res. 1982; 140(2):471-6. DOI: 10.1016/0014-4827(82)90144-6. View

Omoto C, Kung C . Rotation and twist of the central-pair microtubules in the cilia of Paramecium. J Cell Biol. 1980; 87(1):33-46. PMC: 2110732. DOI: 10.1083/jcb.87.1.33. View

10.

Bowne-Anderson H, Hibbel A, Howard J . Regulation of Microtubule Growth and Catastrophe: Unifying Theory and Experiment. Trends Cell Biol. 2015; 25(12):769-779. PMC: 4783267. DOI: 10.1016/j.tcb.2015.08.009. View

11.

Prevo B, Mangeol P, Oswald F, Scholey J, Peterman E . Functional differentiation of cooperating kinesin-2 motors orchestrates cargo import and transport in C. elegans cilia. Nat Cell Biol. 2015; 17(12):1536-45. DOI: 10.1038/ncb3263. View

12.

Wloga D, Camba A, Rogowski K, Manning G, Jerka-Dziadosz M, Gaertig J . Members of the NIMA-related kinase family promote disassembly of cilia by multiple mechanisms. Mol Biol Cell. 2006; 17(6):2799-810. PMC: 1474788. DOI: 10.1091/mbc.e05-05-0450. View

13.

Signor D, Wedaman K, Rose L, Scholey J . Two heteromeric kinesin complexes in chemosensory neurons and sensory cilia of Caenorhabditis elegans. Mol Biol Cell. 1999; 10(2):345-60. PMC: 25173. DOI: 10.1091/mbc.10.2.345. View

14.

Roux K, Kim D, Raida M, Burke B . A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells. J Cell Biol. 2012; 196(6):801-10. PMC: 3308701. DOI: 10.1083/jcb.201112098. View

15.

Haycraft C, Banizs B, Aydin-Son Y, Zhang Q, Michaud E, Yoder B . Gli2 and Gli3 localize to cilia and require the intraflagellar transport protein polaris for processing and function. PLoS Genet. 2005; 1(4):e53. PMC: 1270009. DOI: 10.1371/journal.pgen.0010053. View

16.

Gaertig J, Wloga D, Vasudevan K, Guha M, Dentler W . Discovery and functional evaluation of ciliary proteins in Tetrahymena thermophila. Methods Enzymol. 2013; 525:265-84. PMC: 4392907. DOI: 10.1016/B978-0-12-397944-5.00013-4. View

17.

Roof D, Adamian M, Jacobs D, Hayes A . Cytoskeletal specializations at the rod photoreceptor distal tip. J Comp Neurol. 1991; 305(2):289-303. DOI: 10.1002/cne.903050210. View

18.

Mitchell D . Orientation of the central pair complex during flagellar bend formation in Chlamydomonas. Cell Motil Cytoskeleton. 2003; 56(2):120-9. DOI: 10.1002/cm.10142. View

19.

Bacaj T, Lu Y, Shaham S . The conserved proteins CHE-12 and DYF-11 are required for sensory cilium function in Caenorhabditis elegans. Genetics. 2008; 178(2):989-1002. PMC: 2248344. DOI: 10.1534/genetics.107.082453. View

20.

Nelsen E . Transformation in Tetrahymena thermophila. Development of an inducible phenotype. Dev Biol. 1978; 66(1):17-31. DOI: 10.1016/0012-1606(78)90270-1. View