title: FLA8/KIF3B phosphorylation regulates kinesin-II interaction with IFT-B to control IFT entry and turnaround.
abstract: The assembly and maintenance of cilia depends on intraflagellar transport (IFT). Activated IFT motor kinesin-II enters the cilium with loaded IFT particles comprising IFT-A and IFT-B complexes. At the ciliary tip, kinesin-II becomes inactivated, and IFT particles are released. Moreover, the rate of IFT entry is dynamically regulated during cilium assembly. However, the regulatory mechanism of IFT entry and loading/unloading of IFT particles remains elusive. We show that the kinesin-II motor subunit FLA8, a homolog of KIF3B, is phosphorylated on the conserved S663 by a calcium-dependent kinase in Chlamydomonas. This phosphorylation disrupts the interaction between kinesin-II and IFT-B, inactivates kinesin-II and inhibits IFT entry, and is also required for IFT-B unloading at the ciliary tip. Furthermore, our data suggest that the IFT entry rate is controlled by regulation of the cellular level of phosphorylated FLA8. Therefore, FLA8 phosphorylation acts as a molecular switch to control IFT entry and turnaround.
authors.affiliation: MOE Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, China; School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yinwen
authors.initials: Y
authors.lastname: Liang
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yunong
authors.initials: Y
authors.lastname: Pang
authors.affiliation: MOE Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, China; School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: MOE Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, China; School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Zhangfeng
authors.initials: Z
authors.lastname: Hu
authors.affiliation: MOE Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, China; School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Haiteng
authors.initials: H
authors.lastname: Deng
authors.affiliation: MOE Key Laboratory of Protein Science, Tsinghua University, Beijing 100084, China; School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: panjunmin@tsinghua.edu.cn.
authors.forename: Junmin
authors.initials: J
authors.lastname: Pan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D016825:Chlamydomonas reinhardtii / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism; D005407:Flagella / Q000502:physiology*; D018506:Gene Expression Regulation, Plant; D016547:Kinesins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D010940:Plant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D002135:Calcium-Binding Proteins; D010940:Plant Proteins; C074152:kinesin-II; D016547:Kinesins