title: Tubulin glutamylation regulates ciliary motility by altering inner dynein arm activity.
abstract: How microtubule-associated motor proteins are regulated is not well understood. A potential mechanism for spatial regulation of motor proteins is provided by posttranslational modifications of tubulin subunits that form patterns on microtubules. Glutamylation is a conserved tubulin modification [1] that is enriched in axonemes. The enzymes responsible for this posttranslational modification, glutamic acid ligases (E-ligases), belong to a family of proteins with a tubulin tyrosine ligase (TTL) homology domain (TTL-like or TTLL proteins) [2]. We show that in cilia of Tetrahymena, TTLL6 E-ligases generate glutamylation mainly on the B-tubule of outer doublet microtubules, the site of force production by ciliary dynein. Deletion of two TTLL6 paralogs caused severe deficiency in ciliary motility associated with abnormal waveform and reduced beat frequency. In isolated axonemes with a normal dynein arm composition, TTLL6 deficiency did not affect the rate of ATP-induced doublet microtubule sliding. Unexpectedly, the same TTLL6 deficiency increased the velocity of microtubule sliding in axonemes that also lack outer dynein arms, in which forces are generated by inner dynein arms. We conclude that tubulin glutamylation on the B-tubule inhibits the net force imposed on sliding doublet microtubules by inner dynein arms.
authors.affiliation: Department of Cellular Biology, University of Georgia, Athens, GA 30602, USA.
authors.forename: Swati
authors.initials: S
authors.lastname: Suryavanshi
authors.forename: Bernard
authors.initials: B
authors.lastname: Eddé
authors.forename: Laura A
authors.initials: LA
authors.lastname: Fox
authors.forename: Stella
authors.initials: S
authors.lastname: Guerrero
authors.forename: Robert
authors.initials: R
authors.lastname: Hard
authors.forename: Todd
authors.initials: T
authors.lastname: Hennessey
authors.forename: Amrita
authors.initials: A
authors.lastname: Kabi
authors.forename: David
authors.initials: D
authors.lastname: Malison
authors.forename: David
authors.initials: D
authors.lastname: Pennock
authors.forename: Winfield S
authors.initials: WS
authors.lastname: Sale
authors.forename: Dorota
authors.initials: D
authors.lastname: Wloga
authors.forename: Jacek
authors.initials: J
authors.lastname: Gaertig
mesh_terms: D001696:Biomechanical Phenomena; D002923:Cilia / Q000502:physiology*; D004398:Dyneins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D008870:Microtubules; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D013768:Tetrahymena / Q000166:cytology / Q000502:physiology*; D014404:Tubulin / Q000378:metabolism*
chemical_list: D014404:Tubulin; D004398:Dyneins; D010453:Peptide Synthases; C112698:tubulin polyglutamylase