Cypin regulates K63-linked polyubiquitination to shape synaptic content

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Advances Pub Date : 2025-07-11 DOI:10.1126/sciadv.ads5467

Srinivasa R. Gandu, Ana R. Rodriguez, Jared Lamp, Mihir V. Patel, Kiran Madura, Irving E. Vega, Bonnie L. Firestein

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引用次数: 0

Abstract

An open question in neuroscience is how protein posttranslational modifications regulate synaptic site targeting. Polyubiquitination plays a role in proteasome-mediated protein turnover; however, additional functions for specific types of polyubiquitin linkages have been identified. One type of polyubiquitination, K63-polyubiquitin (K63-polyUb), has been studied for its role in signal transduction within the context of cancer, but little has been done to uncover its role regarding neuronal and synaptic function. Here, we report an emerging function for the cytosolic PSD-95 interactor, cypin, in the regulation of synaptic content by K63-polyUb during neuronal development in vitro and in adult mice in vivo. We identify cypin-promoted K63-polyUb on postsynaptic proteins and also find an important role for cypin in presynaptic function. Our work demonstrates that cypin-promoted changes to K63-polyUb can regulate synaptic content and function on both sides of the synapse, adding important insight into basic mechanisms of neuronal signaling.

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Cypin调节k63连接的多泛素化以形成突触内容

神经科学中的一个开放问题是蛋白质翻译后修饰如何调节突触位点靶向。多泛素化在蛋白酶体介导的蛋白周转中起作用；然而，已经确定了特定类型的多泛素连接的附加功能。一种类型的多泛素化，k63 -多泛素素（k63 - polyb），已被研究其在癌症背景下的信号转导中的作用，但很少有研究揭示其在神经元和突触功能中的作用。在这里，我们报道了细胞质PSD-95相互作用素在体外和体内成年小鼠神经元发育过程中对k63 - polyb突触内容的调节中的新功能。我们在突触后蛋白上发现了cypin促进的k63 - polyb，也发现了cypin在突触前功能中的重要作用。我们的工作表明，cypin促进的k63 - polyb的变化可以调节突触两侧的突触内容和功能，为神经元信号传导的基本机制提供了重要的见解。

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

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.