Department of Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen Ø, Denmark.
Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands.
J Cell Sci. 2022 Jun 15;135(12). doi: 10.1242/jcs.259471. Epub 2022 Jun 24.
The kinesin-3 motor KIF13B functions in endocytosis, vesicle transport and regulation of ciliary length and signaling. Direct binding of the membrane-associated guanylate kinase (MAGUK) DLG1 to the MAGUK-binding stalk domain of KIF13B relieves motor autoinhibition and promotes microtubule plus-end-directed cargo transport. Here, we characterize angiomotin (AMOT) isoform 2 (p80, referred to as Ap80) as a novel KIF13B interactor that promotes binding of another MAGUK, the polarity protein and Crumbs complex component PALS1, to KIF13B. Live-cell imaging analysis indicated that Ap80 is concentrated at and recruits PALS1 to the base of the primary cilium, but is not a cargo of KIF13B itself. Consistent with a ciliary function for Ap80, its depletion led to elongated primary cilia and reduced agonist-induced ciliary accumulation of SMO, a key component of the Hedgehog signaling pathway, whereas Ap80 overexpression caused ciliary shortening. Our results suggest that Ap80 activates KIF13B cargo binding at the base of the primary cilium to regulate ciliary length, composition and signaling.
驱动蛋白-3 马达 KIF13B 在胞吞作用、囊泡运输以及纤毛长度和信号转导的调节中发挥作用。膜相关鸟苷酸激酶（MAGUK）DLG1 与 KIF13B 的 MAGUK 结合茎结构域的直接结合，解除了马达的自动抑制作用，并促进了微管正极定向的货物运输。在这里，我们将血管生成素（AMOT）异构体 2（p80，称为 Ap80）鉴定为一种新型的 KIF13B 相互作用蛋白，它促进了另一种 MAGUK，极性蛋白和 Crumbs 复合物成分 PALS1 与 KIF13B 的结合。活细胞成像分析表明，Ap80 集中在初级纤毛的基部并募集 PALS1，但不是 KIF13B 本身的货物。与 Ap80 的纤毛功能一致，其缺失导致初级纤毛伸长和激动剂诱导的 Hedgehog 信号通路关键成分 SMO 在纤毛中的积累减少，而过表达 Ap80 则导致纤毛缩短。我们的结果表明，Ap80 在初级纤毛的基部激活 KIF13B 货物结合，以调节纤毛长度、组成和信号转导。
