title: Kinesin-4 KIF21B is a potent microtubule pausing factor.
abstract: Microtubules are dynamic polymers that in cells can grow, shrink or pause, but the factors that promote pausing are poorly understood. Here, we show that the mammalian kinesin-4 KIF21B is a processive motor that can accumulate at microtubule plus ends and induce pausing. A few KIF21B molecules are sufficient to induce strong growth inhibition of a microtubule plus end in vitro. This property depends on non-motor microtubule-binding domains located in the stalk region and the C-terminal WD40 domain. The WD40-containing KIF21B tail displays preference for a GTP-type over a GDP-type microtubule lattice and contributes to the interaction of KIF21B with microtubule plus ends. KIF21B also contains a motor-inhibiting domain that does not fully block the interaction of the protein with microtubules, but rather enhances its pause-inducing activity by preventing KIF21B detachment from microtubule tips. Thus, KIF21B combines microtubule-binding and regulatory activities that together constitute an autonomous microtubule pausing factor.
authors.affiliation: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands.
authors.forename: Wilhelmina E
authors.initials: WE
authors.lastname: van Riel
authors.affiliation: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands.
authors.forename: Ankit
authors.identifier: 0000-0002-1569-0919
authors.initials: A
authors.lastname: Rai
authors.affiliation: Laboratory of Biomolecular Research, Department of Biology and Chemistry, Paul Scherrer Institut, Villigen PSI, Switzerland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bianchi
authors.affiliation: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands.
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Katrukha
authors.affiliation: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands.
authors.forename: Qingyang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht Institute for Pharmaceutical Sciences and The Netherlands Proteomics Centre, Utrecht University, Utrecht, Netherlands.
authors.forename: Albert Jr
authors.identifier: 0000-0002-2405-4404
authors.initials: AJ
authors.lastname: Heck
authors.affiliation: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands.
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
authors.affiliation: Laboratory of Biomolecular Research, Department of Biology and Chemistry, Paul Scherrer Institut, Villigen PSI, Switzerland.
authors.forename: Michel O
authors.initials: MO
authors.lastname: Steinmetz
authors.affiliation: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands.
authors.forename: Lukas C
authors.identifier: 0000-0001-9418-6739
authors.initials: LC
authors.lastname: Kapitein
authors.affiliation: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Utrecht, Netherlands.
authors.forename: Anna
authors.identifier: 0000-0002-9048-8614
authors.initials: A
authors.lastname: Akhmanova
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D057809:HEK293 Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D025941:Protein Interaction Mapping; D055503:Protein Multimerization
chemical_list: C550348:KIF21B protein, human; D016547:Kinesins
keywords: EB1; KIF21B; Kinesin; Kinesin-4; biophysics; cell biology; human; microtubule dynamics; pausing; structural biology