Institut Curie, Centre de Recherche, Paris 75248, France; Structure and Membrane Compartments, CNRS UMR144, Paris 75248, France.
Institut Curie, Centre de Recherche, Paris 75248, France; Molecular Mechanisms of Intracellular Transport, CNRS UMR144, Paris 75248, France.
Cell Rep. 2014 Feb 13;6(3):445-54. doi: 10.1016/j.celrep.2014.01.002. Epub 2014 Jan 23.
Early endosomes consist of vacuolar sorting and tubular recycling domains that segregate components fated for degradation in lysosomes or reuse by recycling to the plasma membrane or Golgi. The tubular transport intermediates that constitute recycling endosomes function in cell polarity, migration, and cytokinesis. Endosomal tubulation and fission require both actin and intact microtubules, but although factors that stabilize recycling endosomal tubules have been identified, those required for tubule generation from vacuolar sorting endosomes (SEs) remain unknown. We show that the microtubule motor KIF13A associates with recycling endosome tubules and controls their morphogenesis. Interfering with KIF13A function impairs the formation of endosomal tubules from SEs with consequent defects in endosome homeostasis and cargo recycling. Moreover, KIF13A interacts and cooperates with RAB11 to generate endosomal tubules. Our data illustrate how a microtubule motor couples early endosome morphogenesis to its motility and function.
早期内涵体由液泡分拣和管状回收结构域组成,将注定在溶酶体中降解的成分或通过再循环到质膜或高尔基体进行再利用进行分拣。构成回收内涵体的管状运输中间体在细胞极性、迁移和胞质分裂中发挥作用。内涵体的管化和裂变既需要肌动蛋白又需要完整的微管,但尽管已经确定了稳定回收内涵体小管的因素,但用于从小泡分拣内涵体(SE)生成小管的因素仍然未知。我们发现微管马达 KIF13A 与回收内涵体小管相关联,并控制它们的形态发生。干扰 KIF13A 的功能会损害 SE 中内涵体小管的形成,从而导致内涵体稳态和货物回收缺陷。此外,KIF13A 与 RAB11 相互作用并合作生成内涵体小管。我们的数据说明了微管马达如何将早期内涵体形态发生与其运动和功能联系起来。