UNC-16 与 LRK-1 和 WDFY-3 相互作用，调节轴突生长的终止。

IF 3.3 3区生物学

Genetics Pub Date : 2024-04-06 DOI:10.1093/genetics/iyae053

Cody J Drozd, Tamjid A Chowdhury, Christopher C Quinn

{"title":"UNC-16 与 LRK-1 和 WDFY-3 相互作用，调节轴突生长的终止。","authors":"Cody J Drozd, Tamjid A Chowdhury, Christopher C Quinn","doi":"10.1093/genetics/iyae053","DOIUrl":null,"url":null,"abstract":"In humans, MAPK8IP3 (also known as JIP3) is a neurodevelopmental disorder-associated gene. In C. elegans, the UNC-16 ortholog of the MAPK8IP3 protein can regulate the termination of axon growth. However, its role in this process is not well understood. Here, we report that UNC-16 promotes axon termination through a process that includes the LRK-1(LRRK-1/LRRK-2) kinase and the WDFY-3 (WDFY3/Alfy) selective autophagy protein. Genetic analysis suggests that UNC-16 promotes axon termination through an interaction between its RH1 domain and the dynein complex. Loss of unc-16 function causes accumulation of late endosomes specifically in the distal axon. Moreover, we observe synergistic interactions between loss of unc-16 function and disruptors of endolysosomal function, indicating that the endolysosomal system promotes axon termination. We also find that the axon termination defects caused by loss of UNC-16 function require the function of a genetic pathway that includes lrk-1 and wdfy-3, two genes that have been implicated in autophagy. These observations suggest a model where UNC-16 promotes axon termination by interacting with the endolysosomal system to regulate a pathway that includes LRK-1 and WDFY-3.","PeriodicalId":12706,"journal":{"name":"Genetics","volume":"50 1","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"UNC-16 interacts with LRK-1 and WDFY-3 to regulate the termination of axon growth.\",\"authors\":\"Cody J Drozd, Tamjid A Chowdhury, Christopher C Quinn\",\"doi\":\"10.1093/genetics/iyae053\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"In humans, MAPK8IP3 (also known as JIP3) is a neurodevelopmental disorder-associated gene. In C. elegans, the UNC-16 ortholog of the MAPK8IP3 protein can regulate the termination of axon growth. However, its role in this process is not well understood. Here, we report that UNC-16 promotes axon termination through a process that includes the LRK-1(LRRK-1/LRRK-2) kinase and the WDFY-3 (WDFY3/Alfy) selective autophagy protein. Genetic analysis suggests that UNC-16 promotes axon termination through an interaction between its RH1 domain and the dynein complex. Loss of unc-16 function causes accumulation of late endosomes specifically in the distal axon. Moreover, we observe synergistic interactions between loss of unc-16 function and disruptors of endolysosomal function, indicating that the endolysosomal system promotes axon termination. We also find that the axon termination defects caused by loss of UNC-16 function require the function of a genetic pathway that includes lrk-1 and wdfy-3, two genes that have been implicated in autophagy. These observations suggest a model where UNC-16 promotes axon termination by interacting with the endolysosomal system to regulate a pathway that includes LRK-1 and WDFY-3.\",\"PeriodicalId\":12706,\"journal\":{\"name\":\"Genetics\",\"volume\":\"50 1\",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-04-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Genetics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1093/genetics/iyae053\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Genetics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/genetics/iyae053","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

摘要

在人类中，MAPK8IP3（又称 JIP3）是一种神经发育障碍相关基因。在 elegans 中，MAPK8IP3 蛋白的 UNC-16 同源物可以调节轴突生长的终止。然而，人们对它在这一过程中的作用还不甚了解。在这里，我们报告了UNC-16通过一个包括LRK-1（LRRK-1/LRRK-2）激酶和WDFY-3（WDFY3/Alfy）选择性自噬蛋白的过程促进轴突终止。遗传分析表明，UNC-16 通过其 RH1 结构域与动力蛋白复合体之间的相互作用促进轴突终止。unc-16功能的缺失会导致晚期内体的积累，尤其是在轴突远端。此外，我们观察到 unc-16 功能缺失与内溶酶体功能干扰物之间的协同作用，这表明内溶酶体系统促进了轴突终止。我们还发现，UNC-16 功能缺失导致的轴突终止缺陷需要包括 lrk-1 和 wdfy-3 这两个与自噬有关的基因在内的遗传途径发挥作用。这些观察结果表明了一个模型，即 UNC-16 通过与内溶酶体系统相互作用来调节包括 LRK-1 和 WDFY-3 在内的通路，从而促进轴突终止。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

UNC-16 interacts with LRK-1 and WDFY-3 to regulate the termination of axon growth.

In humans, MAPK8IP3 (also known as JIP3) is a neurodevelopmental disorder-associated gene. In C. elegans, the UNC-16 ortholog of the MAPK8IP3 protein can regulate the termination of axon growth. However, its role in this process is not well understood. Here, we report that UNC-16 promotes axon termination through a process that includes the LRK-1(LRRK-1/LRRK-2) kinase and the WDFY-3 (WDFY3/Alfy) selective autophagy protein. Genetic analysis suggests that UNC-16 promotes axon termination through an interaction between its RH1 domain and the dynein complex. Loss of unc-16 function causes accumulation of late endosomes specifically in the distal axon. Moreover, we observe synergistic interactions between loss of unc-16 function and disruptors of endolysosomal function, indicating that the endolysosomal system promotes axon termination. We also find that the axon termination defects caused by loss of UNC-16 function require the function of a genetic pathway that includes lrk-1 and wdfy-3, two genes that have been implicated in autophagy. These observations suggest a model where UNC-16 promotes axon termination by interacting with the endolysosomal system to regulate a pathway that includes LRK-1 and WDFY-3.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Genetics 生物-遗传学

CiteScore

6.20

自引率

6.10%

发文量

177

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.