Kinesin-4 KIF21B is a potent microtubule pausing factor

• Published in: eLife Vol. 6
• Main Authors: van Riel, Wilhelmina E, Rai, Ankit, Bianchi, Sarah, Katrukha, Eugene A, Liu, Qingyang, Heck, Albert Jr, Hoogenraad, Casper C, Steinmetz, Michel O, Kapitein, Lukas C, Akhmanova, Anna
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 14.03.2017; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Animals; Biology; Biophysics and Structural Biology; Cell Biology; Cercopithecus aethiops; COS Cells; EB1; Glycerol; Growth rate; Guanosine triphosphate; Health aspects; HEK293 Cells; Humans; KIF21B; Kinesin; Kinesin - metabolism; Kinesin-4; Mass spectrometry; Microscopy; microtubule dynamics; Microtubules; Microtubules - metabolism; Mutation; pausing; Polymerization; Polymers; Protein Binding; Protein Domains; Protein Interaction Mapping; Protein Multimerization; Proteins; Proteomics; Scientific imaging; cell biology; EB1; pausing; microtubule dynamics; structural biology; KIF21B; biophysics; human; Kinesin; Kinesin-4
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.24746

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.