KIF13B 通过高尔基体到质膜的 VEGFR2 运输来调节血管生成。
KIF13B regulates angiogenesis through Golgi to plasma membrane trafficking of VEGFR2.
机构信息
Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA Center of Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
Department of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
出版信息
J Cell Sci. 2014 Oct 15;127(Pt 20):4518-30. doi: 10.1242/jcs.156109. Epub 2014 Aug 15.
Although the trafficking of newly synthesized VEGFR2 to the plasma membrane is a key determinant of angiogenesis, the molecular mechanisms of Golgi to plasma membrane trafficking are unknown. Here, we have identified a key role of the kinesin family plus-end molecular motor KIF13B in delivering VEGFR2 cargo from the Golgi to the endothelial cell surface. KIF13B is shown to interact directly with VEGFR2 on microtubules. We also observed that overexpression of truncated versions of KIF13B containing the binding domains that interact with VEGFR2 inhibited VEGF-induced capillary tube formation. KIF13B depletion prevented VEGF-mediated endothelial migration, capillary tube formation and neo-vascularization in mice. Impairment in trafficking induced by knockdown of KIF13B shunted VEGFR2 towards the lysosomal degradation pathway. Thus, KIF13B is an essential molecular motor required for the trafficking of VEGFR2 from the Golgi, and its delivery to the endothelial cell surface mediates angiogenesis.
尽管新合成的 VEGFR2 向质膜的转运是血管生成的关键决定因素，但高尔基体到质膜转运的分子机制尚不清楚。在这里，我们发现驱动蛋白家族的正极分子马达 KIF13B 在将 VEGFR2 货物从高尔基体递送到内皮细胞表面方面起着关键作用。结果表明，KIF13B 直接与微管上的 VEGFR2 相互作用。我们还观察到，过表达包含与 VEGFR2 相互作用的结合结构域的截断形式的 KIF13B 抑制了 VEGF 诱导的毛细血管管形成。KIF13B 耗竭可防止 VEGF 介导的内皮细胞迁移、毛细血管管形成和新血管生成。通过敲低 KIF13B 引起的转运受损会将 VEGFR2 转向溶酶体降解途径。因此，KIF13B 是一种从高尔基体运输 VEGFR2 所必需的分子马达，其向内皮细胞表面的输送介导了血管生成。
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