Two distinct regulatory pathways govern Cct2-Atg8 binding in the process of solid aggrephagy.

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2024-09-25 DOI:10.1038/s44319-024-00275-7

Yuting Chen, Zhaojie Liu, Yi Zhang, Miao Ye, Yingcong Chen, Jianhua Gao, Juan Song, Huan Yang, Choufei Wu, Weijing Yao, Xue Bai, Mingzhu Fan, Shan Feng, Yigang Wang, Liqin Zhang, Liang Ge, Du Feng, Cong Yi

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引用次数: 0

Abstract

CCT2 serves as an aggrephagy receptor that plays a crucial role in the clearance of solid aggregates, yet the underlying molecular mechanisms by which CCT2 regulates solid aggrephagy are not fully understood. Here we report that the binding of Cct2 to Atg8 is governed by two distinct regulatory mechanisms: Atg1-mediated Cct2 phosphorylation and the interaction between Cct2 and Atg11. Atg1 phosphorylates Cct2 at Ser412 and Ser470, and disruption of these phosphorylation sites impairs solid aggrephagy by hindering Cct2-Atg8 binding. Additionally, we observe that Atg11, an adaptor protein involved in selective autophagy, directly associates with Cct2 through its CC4 domain. Deficiency in this interaction significantly weakens the association of Cct2 with Atg8. The requirement of Atg1-mediated Cct2 phosphorylation and of Atg11 for CCT2-LC3C binding and subsequent aggrephagy is conserved in mammalian cells. These findings provide insights into the crucial roles of Atg1-mediated Cct2 phosphorylation and Atg11-Cct2 binding as key mediators governing the interaction between Cct2 and Atg8 during the process of solid aggrephagy.

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在固体凝集过程中，Cct2-Atg8 的结合受两种不同调控途径的支配。

CCT2 是一种凝集受体，在清除固体聚集物中发挥着至关重要的作用，然而 CCT2 调节固体凝集的基本分子机制尚未完全清楚。在这里，我们报告了 Cct2 与 Atg8 的结合受两种不同调控机制的支配：Atg1 介导的 Cct2 磷酸化和 Cct2 与 Atg11 的相互作用。Atg1 使 Cct2 在 Ser412 和 Ser470 处磷酸化，破坏这些磷酸化位点会阻碍 Cct2 与 Atg8 的结合，从而影响固体凝集。此外，我们还观察到参与选择性自噬的适配蛋白 Atg11 通过其 CC4 结构域直接与 Cct2 结合。缺乏这种相互作用会大大削弱 Cct2 与 Atg8 的结合。在哺乳动物细胞中，Atg1 介导的 Cct2 磷酸化和 Atg11 对 CCT2-LC3C 结合及随后的凝集作用的要求是一致的。这些发现使人们深入了解了 Atg1 介导的 Cct2 磷酸化和 Atg11-Cct2 结合作为 Cct2 和 Atg8 在固体凝集过程中相互作用的关键介质的重要作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.