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CD6 triggers actomyosin cytoskeleton remodeling after binding to its receptor complex.
Borjini, Nozha; Lun, Yu; Jang, Geen-Fu; Crabb, Jack; Chen, Yinghua; Crabb, John; Fox, David A; Ivanov, Andrei I; Lin, Feng.
Afiliación
  • Borjini N; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, United States.
  • Lun Y; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, United States.
  • Jang GF; Cole Eye Institute, Cleveland Clinic, 2042 E 102nd St, Cleveland, OH 44106, United States.
  • Crabb J; Cole Eye Institute, Cleveland Clinic, 2042 E 102nd St, Cleveland, OH 44106, United States.
  • Chen Y; Department of Physiology and Biophysics, Case Western Reserve University, 2210 Circle Dr Robbins Building, Cleveland, OH 44106, United States.
  • Crabb J; Cole Eye Institute, Cleveland Clinic, 2042 E 102nd St, Cleveland, OH 44106, United States.
  • Fox DA; Division of Rheumatology and Clinical Autoimmunity Center of Excellence, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48109, United States.
  • Ivanov AI; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, United States.
  • Lin F; Department of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH 44195, United States.
J Leukoc Biol ; 115(3): 450-462, 2024 02 23.
Article en En | MEDLINE | ID: mdl-37820034
The T cell marker CD6 regulates both T cells and target cells during inflammatory responses by interacting with its receptors. However, only a few receptors binding to the extracellular domains of CD6 have been identified, and cellular events induced by CD6 engagement with its receptors in target cells remain poorly understood. In this study, we identified CD44 as a novel CD6 receptor by proximity labeling and confirmed the new CD6-CD44 interaction by biochemical and biophysical approaches. CD44 and the other 2 known CD6 receptors, CD166 and CDCP1, were distributed diffusely on resting retinal pigment epithelium (RPE) cells but clustered together to form a receptor complex upon CD6 binding. CD6 stimulation induced dramatic remodeling of the actomyosin cytoskeleton in RPE cells mediated by activation of RhoA, and Rho-associated kinase signaling, resulting in increased myosin II phosphorylation. Such actomyosin activation triggered the disassembly of tight junctions responsible for RPE barrier integrity in a process that required all components of the tripartite CD6 receptor complex. These data provided new insights into the mechanisms by which CD6 mediates T cell-driven disruption of tissue barriers during inflammation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Actomiosina / Transducción de Señal Idioma: En Revista: J Leukoc Biol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Actomiosina / Transducción de Señal Idioma: En Revista: J Leukoc Biol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido