title: Different states of integrin LFA-1 aggregation are controlled through its association with tetraspanin CD9.
abstract: The tetraspanin CD9 has been shown to interact with different members of the β1 and β3 subfamilies of integrins, regulating through these interactions cell adhesion, migration and signaling. Based on confocal microscopy co-localization and on co-immunoprecipitation results, we report here that CD9 associates with the β2 integrin LFA-1 in different types of leukocytes including T, B and monocytic cells. This association is resistant to stringent solubilization conditions which, together with data from chemical crosslinking, in situ Proximity Ligation Assays and pull-down experiments, suggest a primary/direct type of interaction mediated by the Large Extracellular Loop of the tetraspanin. CD9 exerts inhibitory effects on the adhesive function of LFA-1 and on LFA-1-dependent leukocyte cytotoxic activity. The mechanism responsible for this negative regulation exerted by CD9 on LFA-1 adhesion does not involve changes in the affinity state of this integrin but seems to be related to alterations in its state of aggregation.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid, Spain; Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Reyes
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Monjas
authors.affiliation: Unidad de Investigación, Hospital Santa Cristina, Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain; Departamento de Biología Molecular, Facultad de Ciencias, Universidad Autonoma de Madrid, 28049 Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Yánez-Mó
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Cardeñes
authors.affiliation: Departamento de Biología Vascular e Inflamación, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain.
authors.forename: Giulia
authors.initials: G
authors.lastname: Morlino
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Gilsanz
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid, Spain.
authors.forename: Yesenia
authors.initials: Y
authors.lastname: Machado-Pineda
authors.affiliation: Departamento de Microbiología I, Area de Inmunología, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Lafuente
authors.affiliation: University of Sheffield Medical School, Sheffield S10 2RX, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Monk
authors.affiliation: Departamento de Biología Vascular e Inflamación, Centro Nacional de Investigaciones Cardiovasculares (CNIC), 28029 Madrid, Spain; Servicio de Inmunología, Hospital de la Princesa, Instituto de Investigación Sanitaria La Princesa (IIS-IP), 28006 Madrid, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Madrid
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), 28049 Madrid, Spain; Departamento de Microbiología I, Area de Inmunología, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain. Electronic address: ccabanas@cbm.csic.es.
authors.forename: Carlos
authors.initials: C
authors.lastname: Cabañas
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008297:Male; D060245:Tetraspanin 29 / Q000378:metabolism*
chemical_list: C554869:CD9 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D060245:Tetraspanin 29
keywords: Adhesion; CD9; Cytotoxicity; Integrin; LFA-1; Tetraspanin