ArticleNature medicine2009
Leukocyte adhesion deficiency-III is caused by mutations in KINDLIN3 affecting integrin activation.
Article in Nature medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers.
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Who cites it
199 citing papers in PubMed, 409 citations in OpenAlex.
- Human CalDAG-GEFI gene (RASGRP2) mutation affects platelet function and causes severe bleeding.The Journal of experimental medicine · 2014Trial
- Regulation of cell adhesion and migration by Kindlin-3 cleavage by calpain.The Journal of biological chemistry · 2012Trial
- CRISPR/Cas9-mediated loss of FERMT3 reveals kindlin-3-independent neutrophil activity in LAD-III.Journal of human immunity · 2026Article
- Beyond Integrin Activation: Kindlin-3 as an Organiser of Immune Receptor Signalling.International journal of molecular sciences · 2026Review
- Structural basis of kindlin-3 in leukocyte adhesion deficiency III.Journal of thrombosis and haemostasis : JTH · 2026Article
- Kindlin-3 sustains cytokine interleukin-2 signaling by linking its receptor to integrin LFA-1.The Journal of biological chemistry · 2026Article
- Biomarkers for predicting immunotherapy response and resistance in glioblastoma.Frontiers in immunology · 2026Review
- Molecular Pathogenesis of Inherited Platelet Dysfunction.Biomolecules · 2025Review
- The cytoskeletal control of B cell receptor and integrin signaling in normal B cells and chronic lymphocytic leukemia.FEBS letters · 2025Review
- Article
- The scaffold protein CasL restrains membrane blebbing and promotes T cell migration.Journal of cell science · 2025Article
- Hydrophobicity-Driven Disruption Mechanism in Kindlin-3 Induced by Leukocyte Adhesion Deficiency Mutation.ACS omega · 2025Article
- Kindlin-3 phosphorylation is crucial for thrombosis and hemostasisResearch and practice in thrombosis and haemostasis · 2025Article
- The monogenic landscape of human infectious diseases.The Journal of allergy and clinical immunology · 2025Review
- Article
- Nanoscopy reveals integrin clustering reliant on kindlin-3 but not talin-1.Cell communication and signaling : CCS · 2025Article
- Myosin light chain 6 (Myl6) interacts with kindlin-3 and is required to support integrin αJournal of thrombosis and haemostasis : JTH · 2024Article
- Inactivation of kindlin-3 increases human melanoma aggressiveness through the collagen-activated tyrosine kinase receptor DDR1.Oncogene · 2024Article
- Extracellular vesicles as tools and targets in therapy for diseases.Signal transduction and targeted therapy · 2024Review
- A novel leukocyte adhesion deficiency type III mutation manifests functional importance of the compact FERM domain in kindlin-3.Journal of thrombosis and haemostasis : JTH · 2024Article
139 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Integrins are the major adhesion receptors of leukocytes and platelets. Beta1 and beta2 integrin function on leukocytes is crucial for a successful immune response and the platelet integrin alpha(IIb)beta3 initiates the process of blood clotting through binding fibrinogen. Integrins on circulating cells bind poorly to their ligands but become active after 'inside-out' signaling through other membrane receptors. Subjects with leukocyte adhesion deficiency-1 (LAD-I) do not express beta2 integrins because of mutations in the gene specifying the beta2 subunit, and they suffer recurrent bacterial infections. Mutations affecting alpha(IIb)beta3 integrin cause the bleeding disorder termed Glanzmann's thrombasthenia. Subjects with LAD-III show symptoms of both LAD-I and Glanzmann's thrombasthenia. Their hematopoietically-derived cells express beta1, beta2 and beta3 integrins, but defective inside-out signaling causes immune deficiency and bleeding problems. The LAD-III lesion has been attributed to a C --> A mutation in the gene encoding calcium and diacylglycerol guanine nucleotide exchange factor (CALDAGGEF1; official symbol RASGRP2) specifying the CALDAG-GEF1 protein, but we show that this change is not responsible for the LAD-III disorder. Instead, we identify mutations in the KINDLIN3 (official symbol FERMT3) gene specifying the KINDLIN-3 protein as the cause of LAD-III in Maltese and Turkish subjects. Two independent mutations result in decreased KINDLIN3 messenger RNA levels and loss of protein expression. Notably, transfection of the subjects' lymphocytes with KINDLIN3 complementary DNA but not CALDAGGEF1 cDNA reverses the LAD-III defect, restoring integrin-mediated adhesion and migration.
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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.