ArticleCell reports2023
Distinct bidirectional regulation of LFA1 and α4β7 by Rap1 and integrin adaptors in T cells under shear flow.
Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Targeting Rap1-YAP1 mechanosignaling for ameliorating acute IOP elevation-induced trabecular meshwork dysfunction.iScience · 2026Article
- A Rasa3-Gαi signaling axis orchestrates B lymphocyte trafficking into and through lymphoid organs.Cell reports · 2026Article
- Emerging Potential of Ras-proximate-1 (Rap1) in Mediating Neurodegenerative Diseases.Current neuropharmacology · 2026Review
- Biomechanical signaling of cytoskeleton and membrane reorganization in tumor immune chemotactic migration.Theranostics · 2026Review
- Mechanotransduction in Shaping Immunity: Pathways, Crosstalk, and Pathophysiological Relevance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- The autophagy component LC3 regulates lymphocyte adhesion via LFA1 transport in response to outside-in signaling.Nature communications · 2025Article
- Exclusion of PD-1 from the immune synapse: A novel strategy to modulate T cell function.Molecular therapy. Oncology · 2024Article
- Low-affinity LFA1-dependent outside-in signaling mediates avidity modulation via the Rabin8-Rab8 axis.PNAS nexus · 2024Article
- Mind the GAP: RASA2 and RASA3 GTPase-activating proteins as gatekeepers of T cell activation and adhesion.Trends in immunology · 2023Review
- Article
- The critical role of Rap1-GAPs Rasa3 and Sipa1 in T cells for pulmonary transit and egress from the lymph nodes.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Bidirectional control of integrin activation plays crucial roles in cell adhesive behaviors, but how integrins are specifically regulated by inside-out and outside-in signaling has not been fully understood. Here, we report distinct bidirectional regulation of major lymphocyte homing receptors LFA1 and α4β7 in primary T cells. A small increase of Rap1 activation in L-selectin-mediated tether/rolling was boosted by the outside-in signaling from ICAM1-interacting LFA1 through subsecond, simultaneous activation of Rap1 GTPase and talin1, but not kindlin-3, resulting in increased capture and slowing. In contrast, none of them were required for tether/rolling by α4β7 on MAdCAM1. High Rap1 activation with chemokines or the loss of Rap1-inactivating proteins Rasa3 and Sipa1 increased talin1/kindlin-3-dependent arrest with high-affinity binding of LFA1 to membrane-anchored ICAM1. However, despite increased affinity of α4β7, activated Rap1 severely suppressed adhesion on MAdCAM1 under shear flow, indicating the critical importance of a sequential outside-in/inside-out signaling for α4β7.
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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.