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Background <p>The <i>Dictyostelium</i> 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 <i>tgrB1</i> and inactivating mutations in <i>rapgapB</i>, a regulator of the GTPase protein RapA. Inactivation of either <i>tgrB1</i>, <i>tgrC1</i>, or <i>rapgapB</i> leads to developmental defects, but the respective double-mutant strains <i>rapgapB</i><sup><i>–</i></sup><i>tgrB1</i><sup><i>–</i></sup> and <i>rapgapB</i><sup><i>–</i></sup><i>tgrC1</i><sup><i>–</i></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> Results <p>Here, we show that the mutual suppression between <i>rapgapB</i><sup><i>–</i></sup> and <i>tgrB1</i><sup><i>–</i></sup> restores wild-type development. We also analyzed an activated <i>tgrB1</i> 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 <i>rapgapB</i><sup><i>–</i></sup><i>tgrB1</i><sup><i>–</i></sup> and the activated <i>tgrB1</i> mutation exhibited near wild-type transcriptomes. Our findings suggest that <i>tgrB1</i>, <i>tgrC1</i>, and <i>rapgapB</i> are involved in a pathway in which <i>rapgapB</i> negatively regulates <i>tgrB1</i> and <i>tgrC1</i> expression, whereas <i>tgrB1</i> and <i>tgrC1</i> positively regulate <i>rapgapB</i> expression.</p> Conclusions <p>These findings suggest that the <i>Dictyostelium</i> 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>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月5日

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  • Mariko Katoh-Kurasawa,
  • Lena Trnovec,
  • Peter Lehmann,
  • Blaž Zupan,
  • Gad Shaulsky

摘要

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.