ArticlePLoS biology2006
Hem-1 complexes are essential for Rac activation, actin polymerization, and myosin regulation during neutrophil chemotaxis.
Article in PLoS biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 2 of them syntheses that pooled it.
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Who cites it
119 citing papers in PubMed, 2 syntheses or guidelines pooled it, 184 citations in OpenAlex.
- Using meta-analysis and machine learning to investigate the transcriptional response of immune cells to Leishmania infection.PLoS neglected tropical diseases · 2024Pooled it
- A meta-analysis indicates that the regulation of cell motility is a non-intrinsic function of chemoattractant receptors that is governed independently of directional sensing.Frontiers in immunology · 2022Pooled it
- The actin regulatory protein HS1 interacts with Arp2/3 and mediates efficient neutrophil chemotaxis.The Journal of biological chemistry · 2012Trial
- Functional genomic profiling of schizophrenia-associated genes reveals key microglial regulators.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Alterations of actin in aging.Journal of cell science · 2026Review
- NCKAP1 coordinates focal adhesion and adherens junction dynamics in endothelial barrier maintenance and angiogenesis.iScience · 2026Article
- Functional Genomic Profiling of Schizophrenia-Associated Genes Reveals Key Microglial Regulators.bioRxiv : the preprint server for biology · 2025Article
- Spatial distribution of cytoskeleton-mediated feedback controls cell polarization: A computational study.PLoS computational biology · 2025Article
- WAVE complex forms linear arrays at negative membrane curvature to instruct lamellipodia formation.The Journal of cell biology · 2025Article
- Complementary cytoskeletal feedback loops control signal transduction excitability and cell polarity.Nature communications · 2025Article
- Spatial distribution of cytoskeleton-mediated feedback controls cell polarization: a computational study.bioRxiv : the preprint server for biology · 2025Article
- HNF3α Targets Nckap1l and Promotes Renal Fibrosis Following Ischemia-Reperfusion Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Bioinformatics Approach to Investigating the Immuno-Inflammatory Mechanisms of Periodontitis in the Progression of Atherosclerosis.Current issues in molecular biology · 2025Article
- Neutrophil diversity and function in health and disease.Signal transduction and targeted therapy · 2024Review
- Spatiotemporal transcriptomic mapping of regenerative inflammation in skeletal muscle reveals a dynamic multilayered tissue architecture.The Journal of clinical investigation · 2024Article
- Hem1 is essential for ruffled border formation in osteoclasts and efficient bone resorption.Scientific reports · 2024Article
- Hem1 inborn errors of immunity: waving goodbye to coordinated immunity in mice and humans.Frontiers in immunology · 2024Review
- WAVE2 Regulates Actin-Dependent Processes Induced by the B Cell Antigen Receptor and Integrins.Cells · 2023Article
- Molecular complex detection in protein interaction networks through reinforcement learning.BMC bioinformatics · 2023Article
- Role of NCKAP1 in the Defective Phagocytic Function of Microglia-Like Cells Derived from Rapidly Progressing Sporadic ALS.Molecular neurobiology · 2023Article
59 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
Migrating cells need to make different actin assemblies at the cell's leading and trailing edges and to maintain physical separation of signals for these assemblies. This asymmetric control of activities represents one important form of cell polarity. There are significant gaps in our understanding of the components involved in generating and maintaining polarity during chemotaxis. Here we characterize a family of complexes (which we term leading edge complexes), scaffolded by hematopoietic protein 1 (Hem-1), that organize the neutrophil's leading edge. The Wiskott-Aldrich syndrome protein family Verprolin-homologous protein (WAVE)2 complex, which mediates activation of actin polymerization by Rac, is only one member of this family. A subset of these leading edge complexes are biochemically separable from the WAVE2 complex and contain a diverse set of potential polarity-regulating proteins. RNA interference-mediated knockdown of Hem-1-containing complexes in neutrophil-like cells: (a) dramatically impairs attractant-induced actin polymerization, polarity, and chemotaxis; (b) substantially weakens Rac activation and phosphatidylinositol-(3,4,5)-tris-phosphate production, disrupting the (phosphatidylinositol-(3,4,5)-tris-phosphate)/Rac/F-actin-mediated feedback circuit that organizes the leading edge; and (c) prevents exclusion of activated myosin from the leading edge, perhaps by misregulating leading edge complexes that contain inhibitors of the Rho-actomyosin pathway. Taken together, these observations show that versatile Hem-1-containing complexes coordinate diverse regulatory signals at the leading edge of polarized neutrophils, including but not confined to those involving WAVE2-dependent actin polymerization.
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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.