ArticleThe Journal of cell biology2021
Leep1 interacts with PIP3 and the Scar/WAVE complex to regulate cell migration and macropinocytosis.
Article in The Journal of cell biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- The Proteome ofProteomes · 2026Article
- WAVE complex forms linear arrays at negative membrane curvature to instruct lamellipodia formation.The Journal of cell biology · 2025Article
- GαInternational journal of molecular sciences · 2025Article
- Leep2A and Leep2B function as a RasGAP complex to regulate macropinosome formation.The Journal of cell biology · 2024Article
- Making cups and rings: the 'stalled-wave' model for macropinocytosis.Biochemical Society transactions · 2024Review
- Loss of Myo19 increases metastasis by enhancing microenvironmental ROS gradient and chemotaxis.EMBO reports · 2024Article
- Formation and closure of macropinocytic cups in Dictyostelium.Current biology : CB · 2023Article
- GxcM-Fbp17/RacC-WASP signaling regulates polarized cortex assembly in migrating cells via Arp2/3.The Journal of cell biology · 2023Article
- Orchestration of synaptic functions by WAVE regulatory complex-mediated actin reorganization.Experimental & molecular medicine · 2023Review
- CYRI proteins: controllers of actin dynamics in the cellular 'eat vs walk' decision.Biochemical Society transactions · 2023Review
- Unravelling cell migration: defining movement from the cell surface.Cell adhesion & migration · 2022Review
- Gradients of PI(4,5)PFrontiers in cell and developmental biology · 2022Article
- Crosstalk between circRNAs and the PI3K/AKT signaling pathway in cancer progression.Signal transduction and targeted therapy · 2021Review
- Moving the Research Forward: The Best of British Biology Using the Tractable Model SystemCells · 2021Review
- How Phagocytes Acquired the Capability of Hunting and Removing Pathogens From a Human Body: Lessons Learned From Chemotaxis and Phagocytosis ofFrontiers in cell and developmental biology · 2021Review
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Polarity is essential for diverse functions in many cell types. Establishing polarity requires targeting a network of specific signaling and cytoskeleton molecules to different subregions of the cell, yet the full complement of polarity regulators and how their activities are integrated over space and time to form morphologically and functionally distinct domains remain to be uncovered. Here, by using the model system Dictyostelium and exploiting the characteristic chemoattractant-stimulated translocation of polarly distributed molecules, we developed a proteomic screening approach, through which we identified a leucine-rich repeat domain-containing protein we named Leep1 as a novel polarity regulator. We combined imaging, biochemical, and phenotypic analyses to demonstrate that Leep1 localizes selectively at the leading edge of cells by binding to PIP3, where it modulates pseudopod and macropinocytic cup dynamics by negatively regulating the Scar/WAVE complex. The spatiotemporal coordination of PIP3 signaling, Leep1, and the Scar/WAVE complex provides a cellular mechanism for organizing protrusive structures at the leading edge.
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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.