RABR-1, an atypical Rab-related GTPase, cell-nonautonomously restricts somatosensory dendrite branching.

IF 3.3 3区 生物学 Q2 GENETICS & HEREDITY
Genetics Pub Date : 2024-10-07 DOI:10.1093/genetics/iyae113
Christopher J Salazar, Carlos A Diaz-Balzac, Yu Wang, Maisha Rahman, Barth D Grant, Hannes E Bülow
{"title":"RABR-1, an atypical Rab-related GTPase, cell-nonautonomously restricts somatosensory dendrite branching.","authors":"Christopher J Salazar, Carlos A Diaz-Balzac, Yu Wang, Maisha Rahman, Barth D Grant, Hannes E Bülow","doi":"10.1093/genetics/iyae113","DOIUrl":null,"url":null,"abstract":"<p><p>Neurons are highly polarized cells with dendrites and axons. Dendrites, which receive sensory information or input from other neurons, often display elaborately branched morphologies. While mechanisms that promote dendrite branching have been widely studied, less is known about the mechanisms that restrict branching. Using the nematode Caenorhabditis elegans, we identify rabr-1 (for Rab-related gene 1) as a factor that restricts branching of the elaborately branched dendritic trees of PVD and FLP somatosensory neurons. Animals mutant for rabr-1 show excessively branched dendrites throughout development and into adulthood in areas where the dendrites overlay epidermal tissues. Phylogenetic analyses show that RABR-1 displays similarity to small GTPases of the Rab-type, although based on sequence alone, no clear vertebrate ortholog of RABR-1 can be identified. We find that rabr-1 is expressed and can function in epidermal tissues, suggesting that rabr-1 restricts dendritic branching cell-nonautonomously. Genetic experiments further indicate that for the formation of ectopic branches rabr-1 mutants require the genes of the Menorin pathway, which have been previously shown to mediate dendrite morphogenesis of somatosensory neurons. A translational reporter for RABR-1 reveals a subcellular localization to punctate, perinuclear structures, which correlates with endosomal and autophagosomal markers, but anticorrelates with lysosomal markers suggesting an amphisomal character. Point mutations in rabr-1 analogous to key residues of small GTPases suggest that rabr-1 functions in a GTP-bound form independently of GTPase activity. Taken together, rabr-1 encodes for an atypical small GTPase of the Rab-type that cell-nonautonomously restricts dendritic branching of somatosensory neurons, likely independently of GTPase activity.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457943/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/genetics/iyae113","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
引用次数: 0

Abstract

Neurons are highly polarized cells with dendrites and axons. Dendrites, which receive sensory information or input from other neurons, often display elaborately branched morphologies. While mechanisms that promote dendrite branching have been widely studied, less is known about the mechanisms that restrict branching. Using the nematode Caenorhabditis elegans, we identify rabr-1 (for Rab-related gene 1) as a factor that restricts branching of the elaborately branched dendritic trees of PVD and FLP somatosensory neurons. Animals mutant for rabr-1 show excessively branched dendrites throughout development and into adulthood in areas where the dendrites overlay epidermal tissues. Phylogenetic analyses show that RABR-1 displays similarity to small GTPases of the Rab-type, although based on sequence alone, no clear vertebrate ortholog of RABR-1 can be identified. We find that rabr-1 is expressed and can function in epidermal tissues, suggesting that rabr-1 restricts dendritic branching cell-nonautonomously. Genetic experiments further indicate that for the formation of ectopic branches rabr-1 mutants require the genes of the Menorin pathway, which have been previously shown to mediate dendrite morphogenesis of somatosensory neurons. A translational reporter for RABR-1 reveals a subcellular localization to punctate, perinuclear structures, which correlates with endosomal and autophagosomal markers, but anticorrelates with lysosomal markers suggesting an amphisomal character. Point mutations in rabr-1 analogous to key residues of small GTPases suggest that rabr-1 functions in a GTP-bound form independently of GTPase activity. Taken together, rabr-1 encodes for an atypical small GTPase of the Rab-type that cell-nonautonomously restricts dendritic branching of somatosensory neurons, likely independently of GTPase activity.

RABR-1是一种非典型Rab相关GTPase细胞,它能非自主地限制体感树突的分支。
神经元是具有树突和轴突的高度极化细胞。树突接收来自其他神经元的感觉信息或输入,通常显示出复杂的分支形态。虽然促进树突分枝的机制已被广泛研究,但限制树突分枝的机制却鲜为人知。通过研究线虫秀丽隐杆线虫(Caenorhabditis elegans),我们发现rabr-1(Rab相关基因1)是限制PVD和FLP体感神经元树突分支的一个因子。rabr-1基因突变的动物在整个发育过程中以及成年后,在树突覆盖表皮组织的区域会出现树突过度分枝的现象。系统发育分析表明,RABR-1 与 Rab 型小 GTP 酶具有相似性,但仅根据序列,还不能确定 RABR-1 的脊椎动物直向同源物。我们发现rabr-1在表皮组织中表达并发挥作用,这表明rabr-1非自主地限制树突分枝细胞。遗传实验进一步表明,rabr-1突变体的异位分支的形成需要Menorin通路的基因,这些基因先前已被证明介导了躯体感觉神经元的树突形态发生。RABR-1 的翻译报告物显示,其亚细胞定位为点状、核周结构,与内质体和自噬体标记相关,但与溶酶体标记反相关,表明其具有两体性。rabr-1中类似于小GTP酶关键残基的点突变表明,rabr-1以GTP结合的形式发挥作用,与GTP酶的活性无关。综上所述,rabr-1编码的是一种非典型的Rab型小GTP酶,它能非自主地限制躯体感觉神经元的树突分支,很可能与GTP酶的活性无关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Genetics
Genetics GENETICS & HEREDITY-
CiteScore
6.90
自引率
6.10%
发文量
177
审稿时长
1.5 months
期刊介绍: GENETICS is published by the Genetics Society of America, a scholarly society that seeks to deepen our understanding of the living world by advancing our understanding of genetics. Since 1916, GENETICS has published high-quality, original research presenting novel findings bearing on genetics and genomics. The journal publishes empirical studies of organisms ranging from microbes to humans, as well as theoretical work. While it has an illustrious history, GENETICS has changed along with the communities it serves: it is not your mentor''s journal. The editors make decisions quickly – in around 30 days – without sacrificing the excellence and scholarship for which the journal has long been known. GENETICS is a peer reviewed, peer-edited journal, with an international reach and increasing visibility and impact. All editorial decisions are made through collaboration of at least two editors who are practicing scientists. GENETICS is constantly innovating: expanded types of content include Reviews, Commentary (current issues of interest to geneticists), Perspectives (historical), Primers (to introduce primary literature into the classroom), Toolbox Reviews, plus YeastBook, FlyBook, and WormBook (coming spring 2016). For particularly time-sensitive results, we publish Communications. As part of our mission to serve our communities, we''ve published thematic collections, including Genomic Selection, Multiparental Populations, Mouse Collaborative Cross, and the Genetics of Sex.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信