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Cereblon regulates NK cell cytotoxicity and migration via Rac1 activation.
Fionda, Cinzia; Stabile, Helena; Molfetta, Rosa; Kosta, Andrea; Peruzzi, Giovanna; Ruggeri, Silvia; Zingoni, Alessandra; Capuano, Cristina; Soriani, Alessandra; Paolini, Rossella; Gismondi, Angela; Cippitelli, Marco; Santoni, Angela.
Afiliación
  • Fionda C; Department of Molecular Medicine, Laboratory affiliated to Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
  • Stabile H; Department of Molecular Medicine, Laboratory affiliated to Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
  • Molfetta R; Department of Molecular Medicine, Laboratory affiliated to Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
  • Kosta A; Department of Molecular Medicine, Laboratory affiliated to Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
  • Peruzzi G; Center for Life Nano- & Neuro-Science, Fondazione Istituto Italiano di Tecnologia (IIT), Rome, Italy.
  • Ruggeri S; Department of Molecular Medicine, Laboratory affiliated to Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
  • Zingoni A; Department of Molecular Medicine, Laboratory affiliated to Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
  • Capuano C; Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
  • Soriani A; Department of Molecular Medicine, Laboratory affiliated to Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
  • Paolini R; Department of Molecular Medicine, Laboratory affiliated to Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
  • Gismondi A; Department of Molecular Medicine, Laboratory affiliated to Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
  • Cippitelli M; Department of Molecular Medicine, Laboratory affiliated to Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
  • Santoni A; Department of Molecular Medicine, Laboratory affiliated to Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Italy.
Eur J Immunol ; 51(11): 2607-2617, 2021 11.
Article en En | MEDLINE | ID: mdl-34392531
Rearrangement of the actin cytoskeleton is critical for cytotoxic and immunoregulatory functions as well as migration of natural killer (NK) cells. However, dynamic reorganization of actin is a complex process, which remains largely unknown. Here, we investigated the role of the protein Cereblon (CRBN), an E3 ubiquitin ligase complex co-receptor and the primary target of the immunomodulatory drugs, in NK cells. We observed that CRBN partially colocalizes with F-actin in chemokine-treated NK cells and is recruited to the immunological synapse, thus suggesting a role for this protein in cytoskeleton reorganization. Accordingly, silencing of CRBN in NK cells results in a reduced cytotoxicity that correlates with a defect in conjugate and lytic synapse formation. Moreover, CRBN depletion significantly impairs the ability of NK cells to migrate and reduces the enhancing effect of lenalidomide on NK cell migration. Finally, we provided evidence that CRBN is required for activation of the small GTPase Rac1, a critical mediator of cytoskeleton dynamics. Indeed, in CRBN-depleted NK cells, chemokine-mediated or target cell-mediated Rac1 activation is significantly reduced. Altogether our data identify a critical role for CRBN in regulating NK cell functions and suggest that this protein may mediate the stimulatory effect of lenalidomide on NK cells.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Asesinas Naturales / Movimiento Celular / Proteína de Unión al GTP rac1 / Citotoxicidad Inmunológica / Ubiquitina-Proteína Ligasas / Proteínas Adaptadoras Transductoras de Señales Límite: Humans Idioma: En Revista: Eur J Immunol Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Alemania
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Asesinas Naturales / Movimiento Celular / Proteína de Unión al GTP rac1 / Citotoxicidad Inmunológica / Ubiquitina-Proteína Ligasas / Proteínas Adaptadoras Transductoras de Señales Límite: Humans Idioma: En Revista: Eur J Immunol Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Alemania