ArticlePLoS biology2020
Optogenetics reveals Cdc42 local activation by scaffold-mediated positive feedback and Ras GTPase.
Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- Constitutively active RAS prolongs Cdc42 signalling, while MAPK signalling is attenuated during fission yeast mating.PLoS genetics · 2026Article
- Distinct Cdc42 protein levels differentially regulate polarized growth and cell fusion in Schizosaccharomyces pombe.PLoS biology · 2026Article
- Rax1/2 promote memory of growth by early Ras1 activation to maintain polarity across generations.bioRxiv : the preprint server for biology · 2025Article
- Lighting up yeast: overview of optogenetics in yeast and their applications to yeast biotechnology.FEMS yeast research · 2025Review
- Cdc42 mobility and membrane flows regulate fission yeast cell shape and survival.Nature communications · 2024Article
- Arp2/3-dependent endocytosis ensures Cdc42 oscillations by removing Pak1-mediated negative feedback.The Journal of cell biology · 2024Article
- Patterning of the cell cortex by Rho GTPases.Nature reviews. Molecular cell biology · 2024Review
- The Arp2/3 complex promotes periodic removal of Pak1-mediated negative feedback to facilitate anticorrelated Cdc42 oscillations.bioRxiv : the preprint server for biology · 2023Article
- Redundancy and the role of protein copy numbers in the cell polarization machinery of budding yeast.Nature communications · 2023Article
- Targeting small GTPases: emerging grasps on previously untamable targets, pioneered by KRAS.Signal transduction and targeted therapy · 2023Review
- Reconstitution of a Reversible Membrane Switch via Prenylation by One-Pot Cell-Free Expression.ACS synthetic biology · 2023Article
- The Cdc42 GAP Rga6 promotes monopolar outgrowth of spores.The Journal of cell biology · 2023Article
- Optogenetic modulation of guanine nucleotide exchange factors of Ras superfamily proteins directly controls cell shape and movement.Frontiers in cell and developmental biology · 2023Article
- Chaperone-Dependent Degradation of Cdc42 Promotes Cell Polarity and Shields the Protein from Aggregation.Molecular and cellular biology · 2023Article
- Condensation of the fusion focus by the intrinsically disordered region of the formin Fus1 is essential for cell-cell fusion.Current biology : CB · 2022Article
- Spatial models of pattern formation during phagocytosis.PLoS computational biology · 2022Article
- Orientation of Cell Polarity by Chemical Gradients.Annual review of biophysics · 2022Review
- Designing Single-Component Optogenetic Membrane Recruitment Systems: The Rho-Family GTPase Signaling Toolbox.ACS synthetic biology · 2022Article
- Cdc42 reactivation at growth sites is regulated by local cell-cycle-dependent loss of its GTPase-activating protein Rga4 in fission yeast.Journal of cell science · 2021Article
- Cdc42 GTPase-activating proteins (GAPs) regulate generational inheritance of cell polarity and cell shape in fission yeast.Molecular biology of the cell · 2021Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Local activity of the small GTPase Cdc42 is critical for cell polarization. Whereas scaffold-mediated positive feedback was proposed to break symmetry of budding yeast cells and produce a single zone of Cdc42 activity, the existence of similar regulation has not been probed in other organisms. Here, we address this problem using rod-shaped cells of fission yeast Schizosaccharomyces pombe, which exhibit zones of active Cdc42-GTP at both cell poles. We implemented the CRY2-CIB1 optogenetic system for acute light-dependent protein recruitment to the plasma membrane, which allowed to directly demonstrate positive feedback. Indeed, optogenetic recruitment of constitutively active Cdc42 leads to co-recruitment of the guanine nucleotide exchange factor (GEF) Scd1 and endogenous Cdc42, in a manner dependent on the scaffold protein Scd2. We show that Scd2 function is dispensable when the positive feedback operates through an engineered interaction between the GEF and a Cdc42 effector, the p21-activated kinase 1 (Pak1). Remarkably, this rewired positive feedback confers viability and allows cells to form 2 zones of active Cdc42 even when otherwise essential Cdc42 activators are lacking. These cells further revealed that the small GTPase Ras1 plays a role in both localizing the GEF Scd1 and promoting its activity, which potentiates the positive feedback. We conclude that scaffold-mediated positive feedback, gated by Ras activity, confers robust polarization for rod-shape formation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.