ArticleNature structural & molecular biology2014
Mechanism of IRSp53 inhibition and combinatorial activation by Cdc42 and downstream effectors.
Article in Nature structural & molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
47 citing papers in PubMed, 79 citations in OpenAlex.
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- Mechanisms of active wetting and fluidification in epithelial cell collectives.Nature materials · 2026Article
- ARIES domains: functional signaling units of type I interferon responses.The FEBS journal · 2025Review
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- Mitf regulates gene expression networks implicated in B cell homeostasis, germinal center responses, and tolerance.Frontiers in immunology · 2024Article
- Reconstitution of the transition from a lamellipodia- to filopodia-like actin network with purified proteins.European journal of cell biology · 2023Article
- Article
- Sensing their plasma membrane curvature allows migrating cells to circumvent obstacles.Nature communications · 2023Article
- Molecular Relay Stations in Membrane Nanotubes: IRSp53 Involved in Actin-Based Force Generation.International journal of molecular sciences · 2023Article
- A NanoCurvS platform for quantitative and multiplex analysis of curvature-sensing proteins.Biomaterials science · 2023Article
- Actin Filaments Couple the Protrusive Tips to the Nucleus through the I-BAR Domain Protein IRSp53 during the Migration of Cells on 1D Fibers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Macrophages modulate stiffness-related foreign body responses through plasma membrane deformation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Ena/VASP clustering at microspike tips involves lamellipodin but not I-BAR proteins, and absolutely requires unconventional myosin-X.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Activated I-BAR IRSp53 clustering controls the formation of VASP-actin-based membrane protrusions.Science advances · 2022Article
- The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer.eLife · 2022Article
- IRSp53 promotes postsynaptic density formation and actin filament bundling.The Journal of cell biology · 2022Article
- Dendrite tapering actuates a self-organizing signaling circuit for stochastic filopodia initiation in neurons.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Dendritic Spine Initiation in Brain Development, Learning and Diseases and Impact of BAR-Domain Proteins.Cells · 2021Review
- Full assembly of HIV-1 particles requires assistance of the membrane curvature factor IRSp53.eLife · 2021Article
- Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling.Nature communications · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The Rho family GTPase effector IRSp53 has essential roles in filopodia formation and neuronal development, but its regulatory mechanism is poorly understood. IRSp53 contains a membrane-binding BAR domain followed by an unconventional CRIB motif that overlaps with a proline-rich region (CRIB-PR) and an SH3 domain that recruits actin cytoskeleton effectors. Using a fluorescence reporter assay, we show that human IRSp53 adopts a closed inactive conformation that opens synergistically with the binding of human Cdc42 to the CRIB-PR and effector proteins, such as the tumor-promoting factor Eps8, to the SH3 domain. The crystal structure of Cdc42 bound to the CRIB-PR reveals a new mode of effector binding to Rho family GTPases. Structure-inspired mutations disrupt autoinhibition and Cdc42 binding in vitro and decouple Cdc42- and IRSp53-dependent filopodia formation in cells. The data support a combinatorial mechanism of IRSp53 activation.
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Registered trials
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.