USP12/46 去泛素酶保护整合素免受 ESCRT 介导的溶酶体降解。

IF 6.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Reports Pub Date : 2024-11-06 DOI:10.1038/s44319-024-00300-9

Kaikai Yu, Guan M Wang, Shiny Shengzhen Guo, Florian Bassermann, Reinhard Fässler

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引用次数: 0

摘要

整合素的功能通过多种机制（包括贩运和降解）受到严格调控。整合素反复被内化，进入内体系统，然后被溶酶体降解或回收到质膜。泛素系统决定了内化蛋白是被降解还是被回收。在这里，我们利用基因筛选和依赖性生物素鉴定来确定控制整合素表面水平的去泛素化酶。我们发现，由 USP12（或同源 USP46）、WDR48 和 WDR20 组成的三元去泛素复合物通过阻止 ESCRT 介导的溶酶体降解来稳定 β1 整合素（Itgb1）。从机理上讲，USP12/46-WDR48-WDR20 复合物能清除早期内体中内化的 Itgb1 胞质尾部的泛素，进而阻止 ESCRT 介导的分选和 Itgb1 降解。

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The USP12/46 deubiquitinases protect integrins from ESCRT-mediated lysosomal degradation.

The functions of integrins are tightly regulated via multiple mechanisms including trafficking and degradation. Integrins are repeatedly internalized, routed into the endosomal system and either degraded by the lysosome or recycled back to the plasma membrane. The ubiquitin system dictates whether internalized proteins are degraded or recycled. Here, we use a genetic screen and proximity-dependent biotin identification to identify deubiquitinase(s) that control integrin surface levels. We find that a ternary deubiquitinating complex, comprised of USP12 (or the homologous USP46), WDR48 and WDR20, stabilizes β1 integrin (Itgb1) by preventing ESCRT-mediated lysosomal degradation. Mechanistically, the USP12/46-WDR48-WDR20 complex removes ubiquitin from the cytoplasmic tail of internalized Itgb1 in early endosomes, which in turn prevents ESCRT-mediated sorting and Itgb1 degradation.

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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.