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p24与Tango1的相互作用确保内质网-高尔基体界面的稳定性和高效运输。

p24-Tango1 interactions ensure ER-Golgi interface stability and efficient transport.

作者信息

Yang Ke, Feng Zhi, Pastor-Pareja José Carlos

机构信息

School of Life Sciences, Tsinghua University , Beijing, China.

Tsinghua-Peking Center for Life Sciences , Beijing, China.

出版信息

J Cell Biol. 2024 May 6;223(5). doi: 10.1083/jcb.202309045. Epub 2024 Mar 12.

DOI:10.1083/jcb.202309045
PMID:38470362
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10932740/
Abstract

The eukaryotic p24 family, consisting of α-, β-, γ- and δ-p24 subfamilies, has long been known to be involved in regulating secretion. Despite increasing interest in these proteins, fundamental questions remain about their role. Here, we systematically investigated Drosophila p24 proteins. We discovered that members of all four p24 subfamilies are required for general secretion and that their localizations between ER exit site (ERES) and Golgi are interdependent in an α→βδ→γ sequence. We also found that localization of p24 proteins and ERES determinant Tango1 requires interaction through their respective GOLD and SH3 lumenal domains, with Tango1 loss sending p24 proteins to the plasma membrane and vice versa. Finally, we show that p24 loss expands the COPII zone at ERES and increases the number of ER-Golgi vesicles, supporting a restrictive role of p24 proteins on vesicle budding for efficient transport. Our results reveal Tango1-p24 interplay as central to the generation of a stable ER-Golgi interface.

摘要

真核生物的p24家族由α -、β -、γ -和δ - p24亚家族组成，长期以来一直被认为参与调节分泌过程。尽管人们对这些蛋白质的兴趣与日俱增，但关于它们的作用仍存在一些基本问题。在这里，我们系统地研究了果蝇的p24蛋白。我们发现，所有四个p24亚家族的成员对于一般分泌都是必需的，并且它们在内质网出口位点（ERES）和高尔基体之间的定位在α→βδ→γ序列中是相互依赖的。我们还发现，p24蛋白和ERES决定因子Tango1的定位需要通过它们各自的GOLD和SH3腔内结构域相互作用，Tango1的缺失会使p24蛋白转运到质膜，反之亦然。最后，我们表明p24的缺失会扩大ERES处的COPII区域，并增加内质网 - 高尔基体囊泡的数量，这支持了p24蛋白在囊泡出芽以实现高效运输方面的限制作用。我们的结果揭示了Tango1 - p24相互作用是形成稳定的内质网 - 高尔基体界面的核心。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46a2/10932740/270efb8da584/JCB_202309045_Fig10.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46a2/10932740/0d343a11ec4e/JCB_202309045_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/46a2/10932740/2056b3bcb151/JCB_202309045_FigS1.jpg
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Acute manipulation and real-time visualization of membrane trafficking and exocytosis in Drosophila.在果蝇中急性操作和实时可视化膜运输和胞吐作用。
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Convergence of secretory, endosomal, and autophagic routes in trans-Golgi-associated lysosomes.跨高尔基体相关溶酶体中分泌、内体和自噬途径的融合。
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