更新于：2024-11-01

SNX25

更新于：2024-11-01

基本信息

别名

SBBI31、SNX25、sorting nexin 25

+ [1]

简介

May be involved in several stages of intracellular trafficking.

关联

项与 SNX25 相关的药物

WO2022114167

专利挖掘

靶点

SNX25

作用机制-

在研机构

Nara Medical University

原研机构

Nara Medical University

在研适应症

神经系统表现

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 SNX25 相关的临床结果

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100 项与 SNX25 相关的转化医学

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0 项与 SNX25 相关的专利（医药）

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项与 SNX25 相关的文献（医药）

2024-09-01·Redox Biology

Redox-modulated SNX25 as a novel regulator of GPCR-G protein signaling from endosomes

Article

作者: Sun, Mingwei ; Du, Ruyue ; Zhang, Xiaofei ; Liu, Jinsong ; Dai, Qiankun ; Xu, Tingting ; Xu, Jinxin ; Zhang, Yulong ; Yin, Menghui ; Dong, Yan ; Yu, Zhijun ; Liu, Cuicui ; Gao, Hanhan

GPCR-G protein signaling from endosomes plays a crucial role in various physiological and pathological processes. However, the mechanism by which endosomal G protein signaling is terminated remains largely unknown. In this study, we aimed to investigate the regulatory mechanisms involved in terminating the signaling of Gα subunits from endosomes. Through structural analysis and cell-based assays, we have discovered that SNX25, a protein that targets endosomes via its PXA or PXC domain, interacts with regulator of G protein signaling (RGS) proteins (including RGS2, RGS4, RGS8, and RGS17) in a redox-regulated manner. The interaction between SNX25 and these RGS proteins enhances their GTPase-accelerating activity towards Gα_i/q and their ability to bind GDP-bound (inactive form) Gα_i/q. As a result, SNX25 recruits these RGS proteins to endosomes, leading to the termination of endosomal Gα_i/q signaling. Furthermore, we have found that the SNX25/RGS complex also exerts a negative regulatory effect on Gα_i/q signaling from the plasma membrane. This is achieved by recruiting Gα_i/q to endosomes and preventing its activation on the plasma membrane. Our findings shed light on the previously unknown role of redox-modulated SNX25 in inhibiting Gα_i/q signaling, thereby uncovering a novel mechanism for terminating Gα_i/q signaling from endosomes. Importantly, this study expands our understanding of the regulation of GPCR-Gα_i/q signaling beyond the plasma membrane.

2023-08-01·Molecular biology of the cell

Interaction of the sorting nexin 25 homologue Snazarus with Rab11 balances endocytic and secretory transport and maintains the ultrafiltration diaphragm in nephrocytes.

Article

作者: Blastyák, András ; Maruzs, Tamás ; Lőrincz, Péter ; Jean, Steve ; Feil-Börcsök, Dalma ; Lakatos, Enikő ; Hargitai, Dávid ; Juhász, Gábor

Proper balance of exocytosis and endocytosis is important for the maintenance of plasma membrane lipid and protein homeostasis. This is especially critical in human podocytes and the podocyte-like Drosophila nephrocytes that both use a delicate diaphragm system with evolutionarily conserved components for ultrafiltration. Here, we show that the sorting nexin 25 homologue Snazarus (Snz) binds to Rab11 and localizes to Rab11-positive recycling endosomes in Drosophila nephrocytes, unlike in fat cells where it is present in plasma membrane/lipid droplet/endoplasmic reticulum contact sites. Loss of Snz leads to redistribution of Rab11 vesicles from the cell periphery and increases endocytic activity in nephrocytes. These changes are accompanied by defects in diaphragm protein distribution that resemble those seen in Rab11 gain-of-function cells. Of note, co-overexpression of Snz rescues diaphragm defects in Rab11 overexpressing cells, whereas snz knockdown in Rab11 overexpressing nephrocytes or simultaneous knockdown of snz and tbc1d8b encoding a Rab11 GTPase-activating protein (GAP) leads to massive expansion of the lacunar system that contains mislocalized diaphragm components: Sns and Pyd/ZO-1. We find that loss of Snz enhances while its overexpression impairs secretion, which, together with genetic epistasis analyses, suggest that Snz counteracts Rab11 to maintain the diaphragm via setting the proper balance of exocytosis and endocytosis.

2023-03-01·Nature Immunology

Macrophages set the bar for acute pain sensitivity

Article

作者: Woolf, Clifford J ; Hakim, Sara

A serendipitous behavioral observation in a mouse line led to the discovery that macrophages modulate acute pain.The macrophage-derived protein SNX25 sets the threshold for acute pain through tonic NGF signaling to cutaneous sensory neurons.

项与 SNX25 相关的新闻（医药）

2023-02-03

·生物谷

Nature Immunology: 真皮巨噬细胞通过SNX25-Nrf2途径调控疼痛敏感性

皮肤经常受到机械创伤的压力。撞击皮肤的感觉刺激由外周感觉神经元编码，可分为低阈值机械感受器和伤害感受器，机械感受器检测无害的触觉刺激，伤害性感受器只对有害刺激做出反应。皮肤经常受到机械创伤的压力。撞击皮肤的感觉刺激由外周感觉神经元编码，可分为低阈值机械感受器和伤害感受器，机械感受器检测无害的触觉刺激，伤害性感受器只对有害刺激做出反应。背根神经节(DRG)的小直径神经元是痛觉神经元，而中到大直径的神经元优先检测低阈值机械刺激。皮肤损伤通过激活的伤害性感受器或驻留在损伤区域或渗透到损伤区域的非神经细胞，包括巨噬细胞、肥大细胞和角质形成细胞，释放炎症介质。组织巨噬细胞可分为神经相关亚群和血管相关亚群。皮肤巨噬细胞的一个亚群与周围神经密切相关，并在受损时促进其再生。在神经病变的情况下，巨噬细胞可以通过感应组织血管紧张素2或补体5a来加速痛觉。图片来源：https://doi.org/10.1038/s41590-022-01418-5 近日，来自奈良医科大学的研究者们在Nature Immunology杂志上发表了题为“Dermal macrophages set pain sensitivity by modulating the amount of tissue NGF through an SNX25–Nrf2 pathway”的文章，该研究揭示了真皮巨噬细胞通过SNX25-Nrf2途径调节组织NGF的数量，从而设定疼痛敏感性。外周神经元和免疫细胞之间的串扰在痛觉中很重要。我们在一个疼痛敏感度降低的转基因小鼠系中发现Snx25是一个疼痛调制基因。在小鼠(Snx25cKO小鼠)中，有条件地删除单核细胞和巨噬细胞中的Snx25，而不是外周感觉神经元中的Snx25，可以降低正常和神经病变条件下的疼痛反应。用Snx25cKO和野生型小鼠进行的骨髓移植表明，巨噬细胞调节了疼痛敏感性。在真皮巨噬细胞中表达分选Nexin(SNX)25通过抑制泛素介导的Nrf2的降解来增强神经营养因子NGF的表达。Nrf2是一种激活NGF转录的转录因子。因此，真皮巨噬细胞通过向真皮产生和分泌NGF来设定痛觉阈值，它们可能与背根神经节巨噬细胞在痛觉感知中起协同作用。机制总结图图片来源：https://doi.org/10.1038/s41590-022-01418-5 在本研究中，研究者展示了SNX25在真皮巨噬细胞(以下简称dMac)中的表达通过抑制泛素介导的Nrf2的降解来诱导NGF的产生。Nrf2是一种Cnc-bZIP转录因子，可以激活NGF mRNA的转录。在dMACs中表达的SNX25通过NGF-TrkA(原肌球蛋白受体激酶A，其受体)信号通路调节正常和疼痛诱导条件下的急性痛觉。因此，巨噬细胞-神经元信号在幼稚皮肤和神经病变或炎症情况下的疼痛处理中非常重要。（生物谷 Bioon.com）参考文献 Tatsuhide Tanaka et al. Dermal macrophages set pain sensitivity by modulating the amount of tissue NGF through an SNX25–Nrf2 pathway. Nat Immunol. 2023 Jan 26. doi: 10.1038/s41590-022-01418-5.