State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Nat Cell Biol. 2021 Jul;23(7):782-795. doi: 10.1038/s41556-021-00704-y. Epub 2021 Jun 28.
Endosome fission is essential for cargo sorting and targeting in the endosomal system. However, whether organelles other than the endoplasmic reticulum (ER) participate in endosome fission through membrane contacts is unknown. Here, we characterize a Golgi-derived vesicle, the SEC14L2 compartment, that plays a unique role in facilitating endosome fission through ternary contacts with endosomes and the ER. Localized to the ER-mediated endosome fission site, the phosphatidylinositol transfer protein SEC14L2 promotes phosphatidylinositol 4-phosphate (PtdIns4P) to phosphatidylinositol 3-phosphate (PtdIns3P) conversion before endosome fission. In the absence of SEC14L2, endosome fission is attenuated and more enlarged endosomes arise due to endosomal accumulation of PtdIns4P and reduction in PtdIns3P. Collectively, our data suggest roles of the Golgi network in ER-associated endosome fission and a mechanism involving ER-endosome contacts in the regulation of endosomal phosphoinositide conversion.
内体裂变对于内体系统中货物的分拣和靶向至关重要。然而，内质网 (ER) 以外的细胞器是否通过膜接触参与内体裂变尚不清楚。在这里，我们描述了一种来源于高尔基体的囊泡，即 SEC14L2 隔室，它通过与内体和 ER 的三元接触，在促进内体裂变方面发挥独特作用。定位于 ER 介导的内体裂变部位，磷酸肌醇转移蛋白 SEC14L2 在内体裂变之前促进磷脂酰肌醇 4-磷酸 (PtdIns4P) 向磷脂酰肌醇 3-磷酸 (PtdIns3P) 的转化。在 SEC14L2 缺失的情况下，内体裂变减弱，由于 PtdIns4P 在囊泡内的积累和 PtdIns3P 的减少，导致内体进一步扩大。总之，我们的数据表明高尔基体网络在 ER 相关内体裂变中的作用，以及涉及 ER-内体接触的机制在调节内体磷酸肌醇转化中的作用。
