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CIL 中的一个新结构域调节 IFITM3 从高尔基体的排出，并揭示了 IFITM3 对分泌途径的调节作用。

A novel domain within the CIL regulates egress of IFITM3 from the Golgi and reveals a regulatory role of IFITM3 on the secretory pathway.

机构信息

Centre International de Recherche en Infectiologie (CIRI), Univ Lyon, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, ENS de Lyon, Lyon, France.

Plateforme IBiSA de Microscopie Electronique, Université de Tours et CHU de Tours, Tours, France.

出版信息

Life Sci Alliance. 2022 Apr 8;5(7). doi: 10.26508/lsa.202101174. Print 2022 Jul.

DOI:10.26508/lsa.202101174
PMID:35396335
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8994042/
Abstract

The InterFeron-Induced TransMembrane proteins (IFITMs) are members of the dispanin/CD225 family that act as broad viral inhibitors by preventing viral-to-cellular membrane fusion. In this study, we uncover egress from the Golgi as an important step in the biology of IFITM3 by identifying the domain that regulates this process and that similarly controls the egress of the dispanins IFITM1 and PRRT2, protein linked to paroxysmal kinesigenic dyskinesia. In the case of IFITM3, high levels of expression of , or mutations in the Golgi egress domain, lead to accumulation of IFITM3 in the Golgi and drive generalized glycoprotein trafficking defects. These defects can be relieved upon incubation with Amphotericin B, compound known to relieve IFITM-driven membrane fusion defects, as well as by v-SNARE overexpression, suggesting that IFITM3 interferes with membrane fusion processes important for Golgi functionalities. The comparison of glycoprotein trafficking in WT versus IFITMs-KO cells indicates that the modulation of the secretory pathway is a novel feature of IFITM proteins. Overall, our study defines a novel domain that regulates the egress of several dispanin/CD225 members from the Golgi and identifies a novel modulatory function for IFITM3.

摘要

干扰素诱导跨膜蛋白（IFITMs）是 dispanin/CD225 家族的成员，通过阻止病毒向细胞膜融合来充当广谱病毒抑制剂。在这项研究中，我们通过鉴定调节这一过程的结构域，揭示了 IFITM3 生物学中的出芽作用是一个重要步骤，该结构域同样控制 dispanin IFITM1 和 PRRT2 的出芽作用，PRRT2 与阵发性运动源性运动障碍有关。在 IFITM3 的情况下，高尔基体出芽结构域的高水平表达或突变导致 IFITM3 在高尔基体中的积累，并导致广义糖蛋白运输缺陷。这些缺陷可以通过与两性霉素 B 孵育得到缓解，两性霉素 B 是一种已知可缓解 IFITM 驱动的膜融合缺陷的化合物，也可以通过 v-SNARE 的过表达得到缓解，这表明 IFITM3 干扰了高尔基体功能所必需的膜融合过程。与 WT 相比，IFITMs-KO 细胞中的糖蛋白运输比较表明，对分泌途径的调节是 IFITM 蛋白的一个新特征。总的来说，我们的研究定义了一个新的结构域，该结构域调节了几种 dispanin/CD225 成员从高尔基体的出芽作用，并确定了 IFITM3 的新调节功能。

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The interesting relationship between APOBEC3 deoxycytidine deaminases and cancer: a long road ahead.APOBEC3 脱氨酶与癌症之间有趣的关系：前路漫漫。
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