更新于：2024-05-01

ZFYVE26

zinc finger FYVE-type containing 26

更新于：2024-05-01

基本信息

别名

FYVE domain-containing centrosomal protein、FYVE-CENT、KIAA0321

+ [5]

简介

Phosphatidylinositol 3-phosphate-binding protein required for the abcission step in cytokinesis: recruited to the midbody during cytokinesis and acts as a regulator of abcission. May also be required for efficient homologous recombination DNA double-strand break repair.

关联

100 项与 ZFYVE26 相关的临床结果

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100 项与 ZFYVE26 相关的转化医学

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0 项与 ZFYVE26 相关的专利（医药）

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121

项与 ZFYVE26 相关的文献（医药）

2024-01-31·Movement disorders : official journal of the Movement Disorder Society

Clinical and Genetic Spectrum in a Large Cohort of Hereditary Spastic Paraplegia.

Article

作者: Yuwen Cao ; Haoran Zheng ; Zeyu Zhu ; Li Yao ; Wotu Tian ; Li Cao

BACKGROUND:

Next-generation sequencing-based molecular assessment has benefited the diagnosis of hereditary spastic paraplegia (HSP) subtypes. However, the clinical and genetic spectrum of HSP due to large fragment deletions/duplications has yet to be fully defined.

OBJECTIVE:

We aim to better characterize the clinical phenotypes and genetic features of HSP and to provide new thoughts on diagnosis.

METHODS:

Whole-exome sequencing (WES) was performed in patients with clinically suspected HSP, followed by multiple ligation-dependent probe amplification (MLPA) sequentially carried out for those with negative findings in known causative genes. Genotype-phenotype correlation analyses were conducted under specific genotypes.

RESULTS:

We made a genetic diagnosis in 60% (162/270) of patients, of whom 48.9% (132/270) had 24 various subtypes due to point mutations (SPG4/SPG11/SPG35/SPG7/SPG10/SPG5/SPG3A/SPG2/SPG76/SPG30/SPG6/SPG9A/SPG12/SPG15/SPG17/SPG18/SPG26/SPG49/SPG55/SPG56/SPG57/SPG62/SPG78/SPG80). Thirty patients were found to have causative rearrangements by MLPA (11.1%), among which SPG4 was the most prevalent (73.3%), followed by SPG3A (16.7%), SPG6 (3.3%), SPG7 (3.3%), and SPG11 (3.3%). Clinical analysis showed that some symptoms were often related to specific subtypes, and rearrangement-related SPG3A patients seemingly had later onset. We observed a presumptive anticipation among SPG4 and SPG3A families due to rearrangement.

CONCLUSIONS:

Based on the largest known Asian HSP cohort, including the largest subgroup of rearrangement-related pedigrees, we gain a comprehensive understanding of the clinical and genetic spectrum of HSP. We propose a diagnostic flowchart to sequentially detect the causative genes in practice. Large fragment mutations account for a considerable proportion of HSP, and thus, MLPA screening acts as a beneficial supplement to routine WES. © 2024 International Parkinson and Movement Disorder Society.

2023-11-01·Arquivos de neuro-psiquiatria

Movement disorders in hereditary spastic paraplegias.

Review

作者: Jose Luiz Pedroso ; Thiago Cardoso Vale ; Julian Letícia de Freitas ; Filipe Miranda Milagres Araújo ; Alex Tiburtino Meira ; Pedro Braga Neto ; Marcondes C França ; Vitor Tumas ; Hélio A G Teive ; Orlando G P Barsottini

BACKGROUND:

Hereditary or familial spastic paraplegias (SPG) comprise a group of genetically and phenotypically heterogeneous diseases characterized by progressive degeneration of the corticospinal tracts. The complicated forms evolve with other various neurological signs and symptoms, including movement disorders and ataxia.

OBJECTIVE:

To summarize the clinical descriptions of SPG that manifest with movement disorders or ataxias to assist the clinician in the task of diagnosing these diseases.

METHODS:

We conducted a narrative review of the literature, including case reports, case series, review articles and observational studies published in English until December 2022.

RESULTS:

Juvenile or early-onset parkinsonism with variable levodopa-responsiveness have been reported, mainly in SPG7 and SPG11. Dystonia can be observed in patients with SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 and SPG76. Tremor is not a frequent finding in patients with SPG, but it is described in different types of SPG, including SPG7, SPG9, SPG11, SPG15, and SPG76. Myoclonus is rarely described in SPG, affecting patients with SPG4, SPG7, SPG35, SPG48, and SPOAN (spastic paraplegia, optic atrophy, and neuropathy). SPG4, SPG6, SPG10, SPG27, SPG30 and SPG31 may rarely present with ataxia with cerebellar atrophy. And autosomal recessive SPG such as SPG7 and SPG11 can also present with ataxia.

CONCLUSION:

Patients with SPG may present with different forms of movement disorders such as parkinsonism, dystonia, tremor, myoclonus and ataxia. The specific movement disorder in the clinical manifestation of a patient with SPG may be a clinical clue for the diagnosis.

2023-10-23·PLoS biology

Spatacsin regulates directionality of lysosome trafficking by promoting the degradation of its partner AP5Z1.

Article

作者: Alexandre Pierga ; Raphaël Matusiak ; Margaux Cauhapé ; Julien Branchu ; Lydia Danglot ; Maxime Boutry ; Frédéric Darios

The endoplasmic reticulum (ER) forms contacts with the lysosomal compartment, regulating lysosome positioning and motility. The movements of lysosomes are controlled by the attachment of molecular motors to their surface. However, the molecular mechanisms by which ER controls lysosome dynamics are still elusive. Here, using mouse brain extracts and mouse embryonic fibroblasts, we demonstrate that spatacsin is an ER-resident protein regulating the formation of tubular lysosomes, which are highly dynamic. Screening for spatacsin partners required for tubular lysosome formation showed spatacsin to act by regulating protein degradation. We demonstrate that spatacsin promotes the degradation of its partner AP5Z1, which regulates the relative amount of spastizin and AP5Z1 at lysosomes. Spastizin and AP5Z1 contribute to regulate tubular lysosome formation, as well as their trafficking by interacting with anterograde and retrograde motor proteins, kinesin KIF13A and dynein/dynactin subunit p150Glued, respectively. Ultimately, investigations in polarized mouse cortical neurons in culture demonstrated that spatacsin-regulated degradation of AP5Z1 controls the directionality of lysosomes trafficking. Collectively, our results identify spatacsin as a protein regulating the directionality of lysosome trafficking.

项与 ZFYVE26 相关的新闻（医药）

2024-03-28

·生物探索

Nature | 中国科学院王晓晨/冯巍发现溶酶体膜分裂因子HPO-27

引言溶酶体是降解和信号传导中心，对体内平衡、发育和衰老至关重要。为了满足不同的细胞需求，溶酶体通过不断的融合和分裂重塑其形态和功能。人们对裂变的分子基础所知甚少。2024年3月27日，中国科学院生物物理研究所王晓晨及冯巍共同通讯在Nature在线发表题为“The HEAT repeat protein HPO-27 is a lysosome fission factor”的研究论文，该研究证明，HEAT重复蛋白HPO-27是一种溶酶体裂变因子。HPO-27的缺失会损害溶酶体的裂变，导致过度的管状网络最终崩溃。HPO-27及其人类同源物MROH1被RAB-7募集到溶酶体中，并在裂解位点富集。超分辨率成像、阴性染色电镜和体外重构实验显示，HPO-27和MROH1分别在蠕虫和哺乳动物细胞中自组装介导溶酶体小管的收缩和断裂，并在体外组装切断支撑的膜管。HPO-27的缺失会影响溶酶体的形态、完整性和降解活性，从而影响动物的发育和寿命。因此，HPO-27和MROH1作为自组装分裂因子维持溶酶体稳态和功能。溶酶体是协调细胞代谢和清除的主要降解细胞器和信号中心。溶酶体功能障碍与代谢紊乱、神经退行性疾病和年龄相关病理有关，这突出了溶酶体在生理和衰老中的重要性。溶酶体经历不断的融合和裂变。它们与其他细胞器融合，获得必需的成分和酸度，接收用于降解的货物，并履行分泌功能。为了平衡这种向内的物质流动，溶酶体进行裂变以保持其稳态的数量、形状、大小、组成和功能，并完成再生。可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体(SNARE)复合物在被RAB-7和/或ARL8效应物拴住后以反式方式组装，以驱动溶酶体与货物递送囊泡融合，对溶酶体膜裂变所知甚少。囊泡形成机制可以聚集在纯化的致密溶酶体上，启动出芽，介导吞噬溶酶体的分解，并参与自溶酶体重组(ALR)产生的小管的形成和裂变。遗传性痉挛性截瘫蛋白SPG11、SPG15和AP5参与溶酶体膜循环。磷脂酰肌醇3-磷酸(PtdIns3P)、磷脂酰肌醇4-磷酸(PtdIns4P)、磷脂酰肌醇4,5-二磷酸(PtdIns(4,5)P2)和磷脂酰肌醇3,4,5-三磷酸(PtdIns(3,5)P2)参与溶酶体通过囊泡或管状中间体的膜出口，但其下游效应物尚不清楚。ARF-pi4kii β阳性囊泡可能调节PtdIns3P信号，促进溶酶体小管分裂。动力蛋白超家族蛋白在许多情况下介导分裂，动力蛋白2在肝细胞脂质吞噬过程中切断ALR小管。然而，作用于溶酶体的裂解分子仍有待鉴定。亨廷顿蛋白，延伸因子，蛋白磷酸酶2A的一个亚基，信号激酶TOR1 (HEAT)重复序列是由短环连接的两亲性α-螺旋对阵列。它们存在于功能多样的真核蛋白中。HEAT以反平行方式排列并堆叠以形成具有大表面积的结构柔性和高弹性螺线管。这些特性对于在各种细胞内环境下形成支架和桥接蛋白质-蛋白质相互作用是重要的。HPO-27在溶酶体裂变中的功能模型（Credit: Nature）该研究确定了HPO-27是一个溶酶体裂解分子。HPO-27作为RAB-7效应物被募集到溶酶体中，介导膜收缩和断裂。因此，HPO-27维持溶酶体的形状、结构完整性和降解功能，这对动物的发育和长寿至关重要。人类同源物MROH1也与溶酶体相关，促进小管裂变。该研究表明HPO-27和MROH1自组装介导膜收缩和断裂。中国科学院生物物理研究所王晓晨研究员和冯巍研究员为本文的共同通讯作者。云南大学和中国科学院生物物理研究所联合培养李乐涛博士、中国科学院生物物理研究所刘希璐博士、博士生杨珊珊为共同第一作者。原文链接https://www-nature-com.libproxy1.nus.edu.sg/articles/s41586-024-07249-8责编|探索君排版|探索君文章来源|“iNature”End往期精选围观一文读透细胞死亡(Cell Death) | 24年Cell重磅综述（长文收藏版）热文Nature | 破除传统：为何我们需要重新思考肿瘤的命名方式热文Nature | 2024年值得关注的七项技术热文Nature | 自身免疫性疾病能被治愈吗？科学家们终于看到了希望热文CRISPR技术进化史 | 24年Cell综述