title: Insights into the structure and function of ciliary and flagellar doublet microtubules: tektins, Ca2+-binding proteins, and stable protofilaments.
abstract: Cilia and flagella are conserved, motile, and sensory cell organelles involved in signal transduction and human disease. Their scaffold consists of a 9-fold array of remarkably stable doublet microtubules (DMTs), along which motor proteins transmit force for ciliary motility and intraflagellar transport. DMTs possess Ribbons of three to four hyper-stable protofilaments whose location, organization, and specialized functions have been elusive. We performed a comprehensive analysis of the distribution and structural arrangements of Ribbon proteins from sea urchin sperm flagella, using quantitative immunobiochemistry, proteomics, immuno-cryo-electron microscopy, and tomography. Isolated Ribbons contain acetylated α-tubulin, β-tubulin, conserved protein Rib45, >95% of the axonemal tektins, and >95% of the calcium-binding proteins, Rib74 and Rib85.5, whose human homologues are related to the cause of juvenile myoclonic epilepsy. DMTs contain only one type of Ribbon, corresponding to protofilaments A11-12-13-1 of the A-tubule. Rib74 and Rib85.5 are associated with the Ribbon in the lumen of the A-tubule. Ribbons contain a single ∼5-nm wide filament, composed of equimolar tektins A, B, and C, which interact with the nexin-dynein regulatory complex. A summary of findings is presented, and the functions of Ribbon proteins are discussed in terms of the assembly and stability of DMTs, ciliary motility, and other microtubule systems.
authors.affiliation: From the Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455, linck001@umn.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Linck
authors.affiliation: the Biology Department and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, and.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Fu
authors.affiliation: the Biology Department and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, and.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Lin
authors.affiliation: From the Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455.
authors.forename: Christna
authors.initials: C
authors.lastname: Ouch
authors.affiliation: From the Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota 55455.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Schefter
authors.affiliation: the Institute of Molecular and Cell Physiology, Medical School, Hannover, 30625 Hannover, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Steffen
authors.affiliation: the Biology Department and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, and.
authors.forename: Peter
authors.initials: P
authors.lastname: Warren
authors.affiliation: the Biology Department and Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, and nicastro@brandeis.edu.
authors.forename: Daniela
authors.initials: D
authors.lastname: Nicastro
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D002923:Cilia / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008868:Microtubule Proteins / Q000737:chemistry* / Q000378:metabolism; D008870:Microtubules / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013081:Sperm Motility / Q000502:physiology; D013082:Sperm Tail / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D047270:Strongylocentrotus purpuratus / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D002135:Calcium-Binding Proteins; D008868:Microtubule Proteins; D046912:Multiprotein Complexes; C044103:tektins
keywords: Calcium-binding Protein; Cell Division; Chemotaxis; Dynein; Epilepsy; Intermediate Filament; Tubulin