ArticleJournal of leukocyte biology2019
The trafficking protein JFC1 regulates Rac1-GTP localization at the uropod controlling neutrophil chemotaxis and in vivo migration.
Article in Journal of leukocyte biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- RPSA-OLFM4 axis governs neutrophil migration against bacterial infection and sepsis.Nature communications · 2026Article
- Nexinhib20 inhibits JFC1-mediated mobilization of a subset of CD11b/CD18+ vesicles decreasing integrin avidity, but does not inhibit Rac1.Journal of leukocyte biology · 2025Article
- Decreased Tiam1-mediated Rac1 activation is responsible for impaired directional persistence of chondrocyte migration in microtia.Journal of cellular and molecular medicine · 2024Article
- Rac1: A Regulator of Cell Migration and a Potential Target for Cancer Therapy.Molecules (Basel, Switzerland) · 2023Review
- Nexinhib20 Inhibits Neutrophil Adhesion and βJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- A U-shaped association between baseline neutrophil count and COVID-19-related mortality: A retrospective cohort study.Journal of medical virology · 2021Observational
- Visualization of integrin molecules by fluorescence imaging and techniques.Biocell : official journal of the Sociedades Latinoamericanas de Microscopia Electronica ... et. al · 2021Article
- Evaluation of active Rac1 levels in cancer cells: A case of misleading conclusions from immunofluorescence analysis.The Journal of biological chemistry · 2020Article
- Imaging of the immune system - towards a subcellular and molecular understanding.Journal of cell science · 2020Review
- Therapeutic targeting of neutrophil exocytosis.Journal of leukocyte biology · 2020Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Neutrophil chemotaxis is essential in responses to infection and underlies inflammation. In neutrophils, the small GTPase Rac1 has discrete functions at both the leading edge and in the retraction of the trailing structure at the cell's rear (uropod), but how Rac1 is regulated at the uropod is unknown. Here, we identified a mechanism mediated by the trafficking protein synaptotagmin-like 1 (SYTL1 or JFC1) that controls Rac1-GTP recycling from the uropod and promotes directional migration of neutrophils. JFC1-null neutrophils displayed defective polarization and impaired directional migration to N-formyl-methionine-leucyl-phenylalanine in vitro, but chemoattractant-induced actin remodeling, calcium signaling and Erk activation were normal in these cells. Defective chemotaxis was not explained by impaired azurophilic granule exocytosis associated with JFC1 deficiency. Mechanistically, we show that active Rac1 localizes at dynamic vesicles where endogenous JFC1 colocalizes with Rac1-GTP. Super-resolution microscopy (STORM) analysis shows adjacent distribution of JFC1 and Rac1-GTP, which increases upon activation. JFC1 interacts with Rac1-GTP in a Rab27a-independent manner to regulate Rac1-GTP trafficking. JFC1-null cells exhibited Rac1-GTP accumulation at the uropod and increased tail length, and Rac1-GTP uropod accumulation was recapitulated by inhibition of ROCK or by interference with microtubule remodeling. In vivo, neutrophil dynamic studies in mixed bone marrow chimeric mice show that JFC1
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