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Clarification of mechanism controlling ciliary length and fluid flow

Discovery of a new microtubule-depolymerizing kinesin, KIF19A

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Graduate School of Medicine / Faculty of Medicine
2012/11/22

Prof. N. Hirokawa and Dr. S. Niwa’s group in the Graduate school of Medicine, University of Tokyo has discovered a new kinesin superfamily molecular motor, KIF19A, which controls the length of cilia.

Microscope image of wild type mouse and KIF19A knockout mouse oviduct. © Nobutaka Hirokawa and Shinsuke Niwa
Cilia in the oviduct of KIF19A knockout mice are 2-3 times as long as those of wild type mice. As a result, female KIF19A knockout mice were infertile due to tubal obstruction.

The cilia, rod-like structures 5-10 micrometer in length, cover the lumen of brain ventricles, trachea and oviducts and move to generate fluid flows in mammals. These ciliary movements generate cerebrospinal fluid flow and transfer ovum from ovary to uterus. Abnormality of ciliary length and motility causes diseases such as hydrocephalus and female infertility, but the mechanism to determine proper length of cilia remained totally unknown.

Professor Hirokawa’s group discovered a new molecular motor KIF19A and found that KIF19A is highly concentrated and localized to the tips of cilia. His group discovered also that KIF19A controls ciliary length by depolymerizing microtubules at the tips of cilia by hydrolyzing ATP. His group further generated KIF19A knockout mice which cannot produce KIF19A and found that cilia in KO mice elongated 2-3 times longer than the wild type mice and could not generate proper fluid flows, which in humans results in phenotypes such as hydrocephalus and female infertility due to fallopian tube obstruction. This study has elucidated the mechanism of ciliary length regulation and provided new ways for the diagnosis and potential therapy for diseases such as hydrocephalus and female infertility.

Press release [PDF] (Japanese)

Paper

Shinsuke Niwa, Kazuo Nakajima, Harukata Miki, Yusuke Minato, Doudou Wang, Nobutaka Hirokawa,
“KIF19A is a microtubule-depolymerizing kinesin for ciliary length control”,
Developmental Cell Online Edition: 2012/11/16AM2:00 (Japan time), doi: 10.1016/j.devcel.2012.10.016.
Article link

リンク

Graduate School of Medicine

Department of Cell Biology and Anatomy

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