ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER.
ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER.
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DOI：
10.1083/jcb.201607055
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发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Schrader M
中科院分区：
文献类型：
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作者：
Costello JL;Castro IG;Hacker C;Schrader TA;Metz J;Zeuschner D;Azadi AS;Godinho LF;Costina V;Findeisen P;Manner A;Islinger M;Schrader M
科斯特洛等人。确定 ACBD5 和 VAPB 是哺乳动物细胞中过氧化物酶体-ER 系链的关键成分。这种束缚复合物的破坏导致过氧化物酶体膜扩张减少和过氧化物酶体运动增加。过氧化物酶体（PO）和内质网（ER）在细胞脂质代谢中合作并形成紧密的结构关联，这在几十年前的超微结构研究中首次观察到。 PO-ER 关联被认为会影响多种生理过程，包括脂质代谢、磷脂交换、代谢物转运、信号传导和 PO 生物发生。尽管内质网区域对细胞代谢至关重要，但内质网区域与 PO 相连的机制尚不清楚，特别是在哺乳动物细胞中。在这里，我们确定 PO 膜蛋白酰基辅酶 A 结合域蛋白 5 (ACBD5) 作为驻留 ER 蛋白囊泡相关膜蛋白相关蛋白 B (VAPB) 的结合伴侣。我们证明 ACBD5-VAPB 相互作用调节 PO-ER 关联。此外，我们证明 PO-ER 关联的丧失会扰乱 PO 膜的扩张并增加 PO 的运动。我们的研究结果揭示了在哺乳动物细胞中建立 PO-ER 关联的第一个分子机制，并报告了 ACBD5 在 PO-ER 束缚中的新功能。
Costello et al. identify ACBD5 and VAPB as key components of a peroxisome–ER tether in mammalian cells. Disruption of this tethering complex leads to reduced peroxisomal membrane expansion and increased peroxisomal movement. Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism and form tight structural associations, which were first observed in ultrastructural studies decades ago. PO–ER associations have been suggested to impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, signaling, and PO biogenesis. Despite their fundamental importance to cell metabolism, the mechanisms by which regions of the ER become tethered to POs are unknown, in particular in mammalian cells. Here, we identify the PO membrane protein acyl-coenzyme A–binding domain protein 5 (ACBD5) as a binding partner for the resident ER protein vesicle-associated membrane protein-associated protein B (VAPB). We show that ACBD5–VAPB interaction regulates PO–ER associations. Moreover, we demonstrate that loss of PO–ER association perturbs PO membrane expansion and increases PO movement. Our findings reveal the first molecular mechanism for establishing PO–ER associations in mammalian cells and report a new function for ACBD5 in PO–ER tethering.