TY - JOUR
T1 - KIF19A Is a Microtubule-Depolymerizing Kinesin for Ciliary Length Control
AU - Niwa, Shinsuke
AU - Nakajima, Kazuo
AU - Miki, Harukata
AU - Minato, Yusuke
AU - Wang, Doudou
AU - Hirokawa, Nobutaka
N1 - Funding Information:
The authors thank T. Yagi (University of Tokyo) for the Chlamydomonas axoneme experiments. The authors also thank H. Fukuda, T. Aizawa, T. Akamatsu, S. Hiromi, and others from the Hirokawa laboratory for discussions and technical assistance. N.H. planned and directed this research. K.N. prepared knockout mice. H.M. cloned KIF19A and prepared the antibody. Y.M. found the localization of KIF19A. D.W. purified the recombinant KIF19A. S.N. performed microscope experiments and biochemical analyses. S.N. and N.H. found the ciliary elongation and prepared the manuscript. This study was supported by Carl Zeiss, JEOL, and a Grant-in-Aid for Specially Promoted Research to N.H. from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
PY - 2012/12/11
Y1 - 2012/12/11
N2 - 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. The mechanism that determines ciliary length is essential for proper fluid flow generation. Niwa et al. find that KIF19A regulates the length of motile cilia by depolymerizing microtubules at ciliary tips. Disruption of this mechanism causes ciliopathy-like phenotypes such as hydrocephalus and female infertility.
AB - 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. The mechanism that determines ciliary length is essential for proper fluid flow generation. Niwa et al. find that KIF19A regulates the length of motile cilia by depolymerizing microtubules at ciliary tips. Disruption of this mechanism causes ciliopathy-like phenotypes such as hydrocephalus and female infertility.
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U2 - 10.1016/j.devcel.2012.10.016
DO - 10.1016/j.devcel.2012.10.016
M3 - Article
C2 - 23168168
AN - SCOPUS:84870839369
SN - 1534-5807
VL - 23
SP - 1167
EP - 1175
JO - Developmental Cell
JF - Developmental Cell
IS - 6
ER -