{"doi":"10.1242/jcs.258602","title":"LFA-1 and kindlin-3 enable the collaborative transport of SLP-76 microclusters by myosin and dynein motors","abstract":"Integrin engagement within the immune synapse enhances T cell activation, but our understanding of this process is incomplete. In response to T cell receptor (TCR) ligation, SLP-76 (LCP2), ADAP (FYB1) and SKAP55 (SKAP1) are recruited into microclusters and activate integrins via the effectors talin-1 and kindlin-3 (FERMT3). We postulated that integrins influence the centripetal transport and signaling of SLP-76 microclusters via these linkages. We show that contractile myosin filaments surround and are co-transported with SLP-76 microclusters, and that TCR ligand density governs the centripetal movement of both structures. Centripetal transport requires formin activity, actomyosin contraction, microtubule integrity and dynein motor function. Although immobilized VLA-4 (α4β1 integrin) and LFA-1 (αLβ2 integrin) ligands arrest the centripetal movement of SLP-76 microclusters and myosin filaments, VLA-4 acts distally, while LFA-1 acts in the lamellum. Integrin β2, kindlin-3 and zyxin are required for complete centripetal transport, while integrin β1 and talin-1 are not. CD69 upregulation is similarly dependent on integrin β2, kindlin-3 and zyxin, but not talin-1. These findings highlight the integration of cytoskeletal systems within the immune synapse and reveal extracellular ligand-independent roles for LFA-1 and kindlin-3. This article has an associated First Person interview with the first author of the paper.","journal":"Journal of Cell Science","year":2021,"id":185705,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9538,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":308828,"name":"Alenka Lovy","orcid":"0000-0002-8167-3199","position":1,"is_corresponding":false},{"id":446786,"name":"Nicholas R. Sylvain","orcid":"0000-0003-4325-1953","position":2,"is_corresponding":false},{"id":742356,"name":"Frank A. Scangarello","orcid":"0000-0002-3993-608X","position":3,"is_corresponding":false},{"id":388580,"name":"Hayley I. Muendlein","orcid":"0000-0003-3006-5780","position":4,"is_corresponding":false},{"id":256199,"name":"Michael Ophir","orcid":"0000-0002-5516-1237","position":5,"is_corresponding":false},{"id":742357,"name":"Ken Nguyen","orcid":"0000-0002-3644-3490","position":6,"is_corresponding":false},{"id":446787,"name":"Maria‐Cristina Seminario","orcid":"0000-0003-0762-8661","position":7,"is_corresponding":false},{"id":446788,"name":"Stephen C. Bunnell","orcid":"0000-0001-6887-0828","position":8,"is_corresponding":false},{"id":54224,"name":"Keith P. Eidell","orcid":"0000-0002-5971-218X","position":0,"is_corresponding":true}],"reference_count":111,"raw_metadata":null,"created_at":"2026-07-18T23:48:38.805613Z","pmid":"34279667","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}