TECPR2 Cooperates with LC3C to Regulate COPII-Dependent ER Export
TECPR2 Cooperates with LC3C to Regulate COPII-Dependent ER Export
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DOI：
10.1016/j.molcel.2015.09.010
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发表时间：
2015-10-01
期刊：
影响因子：
16
通讯作者：
Behrends, Christian
中科院分区：
文献类型：
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作者：
Stadel, Daniela;Millarte, Valentina;Behrends, Christian
遗传性痉挛截瘫(HSPs)是一组以皮质脊髓运动神经元轴索病变为特征的多种神经退行性疾病。Tectoninβ-Proeller Containing Protein 2(TECPR2)编码基因的突变会导致HSP，并伴有神经系统症状。虽然TECPR2是一种人ATG8结合蛋白，也是自噬的正调控因子，但TECPR2的确切功能尚不清楚。在这里，我们证明了TECPR2与几个贩运成分有关，其中包括COPII外壳蛋白SEC24D。TECPR2是稳定SEC24D蛋白水平，维持功能性ER出口位点(ERE)，并以一种依赖于与脂化的LC3C结合的方式有效地输出ER所必需的。TECPR2缺陷的HSP患者细胞表现出SEC24D丰度和ER输出效率的变化。此外，TECPR2和LC3C对于自噬小体的形成是必需的，可能是通过维持ERES的功能来实现的。综上所述，这些结果揭示了TECPR2作为连接早期分泌途径和自噬的分子支架。
Hereditary spastic paraplegias (HSPs) are a diverse group of neurodegenerative diseases that are characterized by axonopathy of the corticospinal motor neurons. A mutation in the gene encoding for Tectonin beta-propeller containing protein 2 (TECPR2) causes HSP that is complicated by neurological symptoms. While TECPR2 is a human ATG8 binding protein and positive regulator of autophagy, the exact function of TECPR2 is unknown. Here, we show that TECPR2 associates with several trafficking components, among them the COPII coat protein SEC24D. TECPR2 is required for stabilization of SEC24D protein levels, maintenance of functional ER exit sites (ERES), and efficient ER export in a manner dependent on binding to lipidated LC3C. TECPR2-deficient HSP patient cells display alterations in SEC24D abundance and ER export efficiency. Additionally, TECPR2 and LC3C are required for autophagosome formation, possibly through maintaining functional ERES. Collectively, these results reveal that TECPR2 functions as molecular scaffold linking early secretion pathway and autophagy.