Multiple Ways to Keep FFAT Under Control!
Multiple Ways to Keep FFAT Under Control!
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DOI：
10.1177/25152564221101219
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发表时间：
2022-01-01
期刊：
影响因子：
--
通讯作者：
Costello JL
中科院分区：
文献类型：
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作者：
Kors S;Schrader M;Costello JL
过氧化物酶体和内质网是紧密相连的细胞器，它们共同参与脂质代谢。在最近发表在《细胞生物学杂志》上的一篇研究论文中，我们描述了一种新的机制，通过磷酸化过氧化物酶体蛋白ACBD5来调节过氧化物酶体-内质网膜接触位点。我们发现ACBD5和内质网蛋白VAPB之间的相互作用是由ACBD5在其FFAT基序的两个不同位点（VAPB结合位点）的磷酸化控制的，我们之前已经证明ACBD5在过氧化物酶体-内质网接触处形成一个系链复合物。我们还发现GSK3-β激酶负责ACBD5的直接磷酸化，以负性调节与VAPB的相互作用，导致过氧化物酶体-内质网接触减少。在本文中，我们结合其他关于VAP相互作用物磷酸化的研究，提供了这一工作原理的额外见解，表明通过磷酸化对FFAT基序进行正调控和负调控的复杂系统。
Peroxisomes and the ER are closely inter-connected organelles, which collaborate in the metabolism of lipids. In a recent research paper in the Journal of Cell Biology, we describe a novel mechanism by which peroxisome-ER membrane contact sites are regulated, via phosphorylation of the peroxisomal protein ACBD5. We found that the interaction between ACBD5 and the ER protein VAPB, which we have previously shown to form a tether complex at peroxisome-ER contacts, is controlled by phosphorylation of ACBD5 at two different sites of its FFAT motif – the VAPB binding site. We also identify the kinase GSK3-β as being responsible for direct phosphorylation of ACBD5 to negatively regulate interaction with VAPB, leading to reduced peroxisome-ER contacts. In this article we provide additional insights into how this work, in combination with other studies on phosphorylation of VAP interactors, suggests a complex system of both positive and negative regulation of the FFAT motif via phosphorylation.