PTEN Negatively Regulates Spastin Ser210 Phosphorylation To Modulate GluA1 Surface Trafficking and Excitatory Synaptic Transmission

IF 4.5 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

ACS Chemical Neuroscience Pub Date : 2026-08-05 Epub Date: 2026-07-17 DOI:10.1021/acschemneuro.6c00114

Danlei Liu, Jiagui Zhong, Laijian Wang, Xiaonan Zhu, Shubin Chen, Jiong Li, Guoqing Guo, Caihui Cha, Jifeng Zhang, Guangyin Yu, Yuchuan Zhong

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引用次数: 0

Abstract

As a key component of the cytoskeleton, microtubule dynamics provide structural support for neurite growth. Spastin plays a critical role in reshaping microtubule arrangement, which is essential for axon development and regeneration. However, the mechanism by which spastin is activated and functions remains unclear. In this study, we discovered that phosphorylation of spastin at Ser210 promotes dendrite growth and surface expression of GluA1 in neurons, enhancing synaptic transmission. Conversely, dephosphorylation of spastin inhibits dendrite growth and surface expression of GluA1, weakening synaptic transmission. PTEN interacts with the MIT domain of spastin through its C-terminal region, resulting in reduced spastin phosphorylation expression levels. This process suppresses the transport of the AMPA receptor GluA1 subunit, thereby modulating neurite outgrowth and weakening synaptic transmission. In conclusion, our research indicates that PTEN is the pathway that regulates the phosphorylation of spastin, providing an important reference for the treatment of neurological diseases characterized by microtubule dysregulation.

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PTEN负调控Spastin Ser210磷酸化调节GluA1表面运输和兴奋性突触传递。

作为细胞骨架的关键组成部分，微管动力学为神经突的生长提供了结构支持。Spastin在重塑微管排列中起关键作用，这对轴突的发育和再生至关重要。然而，痉挛素被激活和发挥作用的机制尚不清楚。在本研究中，我们发现spastin Ser210位点的磷酸化促进神经元树突生长和表面GluA1的表达，增强突触传递。相反，spastin的去磷酸化抑制树突生长和GluA1的表面表达，减弱突触传递。PTEN通过其c端区与spastin的MIT结构域相互作用，导致spastin磷酸化表达水平降低。这一过程抑制AMPA受体GluA1亚基的转运，从而调节神经突生长和减弱突触传递。综上所述，我们的研究表明PTEN是调控spastin磷酸化的通路，为治疗以微管失调为特征的神经系统疾病提供了重要参考。

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来源期刊

ACS Chemical Neuroscience BIOCHEMISTRY & MOLECULAR BIOLOGY-CHEMISTRY, MEDICINAL

CiteScore

9.20

自引率

4.00%

发文量

323

审稿时长

1 months

期刊介绍： ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following: Neurotransmitters and receptors Neuropharmaceuticals and therapeutics Neural development—Plasticity, and degeneration Chemical, physical, and computational methods in neuroscience Neuronal diseases—basis, detection, and treatment Mechanism of aging, learning, memory and behavior Pain and sensory processing Neurotoxins Neuroscience-inspired bioengineering Development of methods in chemical neurobiology Neuroimaging agents and technologies Animal models for central nervous system diseases Behavioral research