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PreprintCited by 5Protein Kinase Regulation and GTPase SignalingFungal and yeast genetics researchGene Regulatory Network Analysis

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Negative feedback regulation of the hemi-arrestin MAPK scaffold Sms1 prevents untimely mating

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Sieber, Boris, Merlini, Laura, Li, Wanlan, Besomi, Maëlys, Michon, Laetitia, Gordon-Lennox, Sushila, Martin, Sophie G·2025·Nature Communications
DOI 10.1101/2025.09.24.678297

Preprint — published as 10.1038/s41467-026-70631-9 · Paper page

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Abstract

Summary: Mitogen-activated protein kinases (MAPK) are ancestral kinases that form essential signalling cascades. However, scaffolds that recruit kinases to subcellular locations and promote signal transduction have only been described in few species. Notably, no scaffold was thought necessary for the MAPK cascade promoting sexual differentiation in fission yeast. Here, we identify the hemi-arrestin protein Sms1 as a structurally novel scaffold of this MAPK cascade. Interactions with PIP2 and the pheromone receptor–coupled Gα subunit target Sms1 to plasma membrane patches, where it assembles the active cascade by binding each MAP kinase. These interactions are essential for signal transduction and local signal interpretation for polarised growth. Phosphorylation, including by the MAPK itself, antagonises Sms1 membrane translocation, establishing a negative feedback that underlies polarity patch turnover and prevents untimely mating attempts. Thus, Sms1 is a MAPK scaffold with canonical functions despite its distinct structural fold, highlighting convergent evolution of MAPK scaffolds across eukaryotes.

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Metadata

Authors
Sieber, B., Merlini, L., Li, W., Besomi, M., Michon, L., Gordon-Lennox, S., & Martin, S. G.
Affiliations
University of Geneva (CH)
Corresponding author
  • Sieber, Boris
  • Martin, Sophie G
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2025-09-25
Volume
17
Issue
1
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2025.09.24.678297
OpenAlex
W7138101677
Cited by
5
References
2
Citations by year
2026: 4 · 2025: 1
FWCI
8.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
Keywords
mitogen-activated protein kinase cascade, pheromone signalling, mating, sexual differentiation, phosphatidylinositol 4,5-bisphosphate, phosphoregulation, membrane translocation, negative feedback, Schizosaccharomyces pombe
MeSH terms
Cell Membrane, Phosphorylation, Schizosaccharomyces, Signal Transduction, Arrestins, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Schizosaccharomyces pombe Proteins

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