Mutual suppression between mutations in the Dictyostelium Greenbeard pathway restores wild-type development.

IF 3.7 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Mariko Katoh-Kurasawa, Lena Trnovec, Peter Lehmann, Blaž Zupan, Gad Shaulsky
{"title":"Mutual suppression between mutations in the Dictyostelium Greenbeard pathway restores wild-type development.","authors":"Mariko Katoh-Kurasawa, Lena Trnovec, Peter Lehmann, Blaž Zupan, Gad Shaulsky","doi":"10.1186/s12864-025-11745-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The Dictyostelium greenbeard pathway is mediated by two polymorphic transmembrane proteins, the TgrC1 ligand and the TgrB1 receptor. These proteins mediate allorecognition, altruism, and the developmental transition to multicellularity. A genetic suppressor screen revealed activating mutations in tgrB1 and inactivating mutations in rapgapB, a regulator of the GTPase protein RapA. Inactivation of either tgrB1, tgrC1, or rapgapB leads to developmental defects, but the respective double-mutant strains rapgapB<sup>-</sup>tgrB1<sup>-</sup> and rapgapB<sup>-</sup>tgrC1<sup>-</sup> develop well and produce spores. This mutual suppression could result from inducing an alternative pathway or from restoring wild-type development, but morphological analyses alone could not resolve this question.</p><p><strong>Results: </strong>Here, we show that the mutual suppression between rapgapB<sup>-</sup> and tgrB1<sup>-</sup> restores wild-type development. We also analyzed an activated tgrB1 allele in the wild-type background and found evidence for interactions between the wild-type and the activated alleles. Using RNA-sequencing analyses, we compared the transcriptomes of the wild type to those of several mutant strains and found that the single-gene mutations attenuated transcriptome progression over developmental time, whereas the double-gene mutation strain rapgapB<sup>-</sup>tgrB1<sup>-</sup> and the activated tgrB1 mutation exhibited near wild-type transcriptomes. Our findings suggest that tgrB1, tgrC1, and rapgapB are involved in a pathway in which rapgapB negatively regulates tgrB1 and tgrC1 expression, whereas tgrB1 and tgrC1 positively regulate rapgapB expression.</p><p><strong>Conclusions: </strong>These findings suggest that the Dictyostelium greenbeard pathway interfaces with the central RapGAPB-RapA regulatory pathway, providing molecular insight into a mutual suppression mechanism in which two deleterious mutations restore wild-type behavior.</p>","PeriodicalId":9030,"journal":{"name":"BMC Genomics","volume":"26 1","pages":"563"},"PeriodicalIF":3.7000,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12142906/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Genomics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s12864-025-11745-0","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOTECHNOLOGY & APPLIED MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background: The Dictyostelium greenbeard pathway is mediated by two polymorphic transmembrane proteins, the TgrC1 ligand and the TgrB1 receptor. These proteins mediate allorecognition, altruism, and the developmental transition to multicellularity. A genetic suppressor screen revealed activating mutations in tgrB1 and inactivating mutations in rapgapB, a regulator of the GTPase protein RapA. Inactivation of either tgrB1, tgrC1, or rapgapB leads to developmental defects, but the respective double-mutant strains rapgapB-tgrB1- and rapgapB-tgrC1- develop well and produce spores. This mutual suppression could result from inducing an alternative pathway or from restoring wild-type development, but morphological analyses alone could not resolve this question.

Results: Here, we show that the mutual suppression between rapgapB- and tgrB1- restores wild-type development. We also analyzed an activated tgrB1 allele in the wild-type background and found evidence for interactions between the wild-type and the activated alleles. Using RNA-sequencing analyses, we compared the transcriptomes of the wild type to those of several mutant strains and found that the single-gene mutations attenuated transcriptome progression over developmental time, whereas the double-gene mutation strain rapgapB-tgrB1- and the activated tgrB1 mutation exhibited near wild-type transcriptomes. Our findings suggest that tgrB1, tgrC1, and rapgapB are involved in a pathway in which rapgapB negatively regulates tgrB1 and tgrC1 expression, whereas tgrB1 and tgrC1 positively regulate rapgapB expression.

Conclusions: These findings suggest that the Dictyostelium greenbeard pathway interfaces with the central RapGAPB-RapA regulatory pathway, providing molecular insight into a mutual suppression mechanism in which two deleterious mutations restore wild-type behavior.

Dictyostelium Greenbeard通路突变间的相互抑制恢复了野生型的发育。
背景:盘基骨菌绿须通路由两种多态跨膜蛋白介导,即TgrC1配体和TgrB1受体。这些蛋白质介导同种异体识别、利他行为和向多细胞的发育过渡。基因抑制筛选显示tgrB1激活突变和rapgapB失活突变,rapapb是GTPase蛋白RapA的调节因子。tgrB1、tgrC1或rapgapB的失活都会导致发育缺陷,但各自的双突变菌株rapgapB-tgrB1-和rapgapB-tgrC1-发育良好并产生孢子。这种相互抑制可能是诱导替代途径或恢复野生型发育的结果,但仅靠形态学分析无法解决这个问题。结果:在这里,我们发现rapgapB-和tgrB1-之间的相互抑制恢复了野生型的发育。我们还分析了野生型背景中激活的tgrB1等位基因,并发现了野生型和激活等位基因之间相互作用的证据。通过rna测序分析,我们比较了野生型和几种突变菌株的转录组,发现单基因突变在发育过程中减弱了转录组的进展,而双基因突变菌株rapgapB-tgrB1-和激活的tgrB1突变表现出接近野生型的转录组。我们的研究结果表明,tgrB1、tgrC1和rapgapB参与了一条途径,其中rapgapB负向调控tgrB1和tgrC1的表达,而tgrB1和tgrC1正向调控rapgapB的表达。结论:这些发现表明Dictyostelium绿须通路与中心RapGAPB-RapA调控通路相互作用,为两种有害突变恢复野生型行为的相互抑制机制提供了分子视角。
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
BMC Genomics
BMC Genomics 生物-生物工程与应用微生物
CiteScore
7.40
自引率
4.50%
发文量
769
审稿时长
6.4 months
期刊介绍: BMC Genomics is an open access, peer-reviewed journal that considers articles on all aspects of genome-scale analysis, functional genomics, and proteomics. BMC Genomics is part of the BMC series which publishes subject-specific journals focused on the needs of individual research communities across all areas of biology and medicine. We offer an efficient, fair and friendly peer review service, and are committed to publishing all sound science, provided that there is some advance in knowledge presented by the work.
×
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:604180095
Book学术官方微信