title: KIF19A is a microtubule-depolymerizing kinesin for ciliary length control.
abstract: Cilia control homeostasis of the mammalian body by generating fluid flow. It has long been assumed that ciliary length-control mechanisms are essential for proper flow generation, because fluid flow generation is a function of ciliary length. However, the molecular mechanisms of ciliary length control in mammals remain elusive. Here, we suggest that KIF19A, a member of the kinesin superfamily, regulates ciliary length by depolymerizing microtubules at the tips of cilia. Kif19a(-/-) mice displayed hydrocephalus and female infertility phenotypes due to abnormally elongated cilia that cannot generate proper fluid flow. KIF19A localized to cilia tips, and recombinant KIF19A controlled the length of microtubules polymerized from axonemes in vitro. KIF19A had ATP-dependent microtubule-depolymerizing activity mainly at the plus end of microtubules. Our results indicated a molecular mechanism of ciliary length regulation in mammals, which plays an important role in the maintenance of the mammalian body.
authors.affiliation: Department of Cell Biology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Niwa
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nakajima
authors.forename: Harukata
authors.initials: H
authors.lastname: Miki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Minato
authors.forename: Doudou
authors.initials: D
authors.lastname: Wang
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hirokawa
mesh_terms: D000818:Animals; D002923:Cilia / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure*; D005260:Female; D006849:Hydrocephalus / Q000235:genetics; D007247:Infertility, Female / Q000235:genetics; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: C578236:KIF19A protein, mouse; D016547:Kinesins