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El S-Geranylgeranyl-L-glutatión es un ligando para el receptor de confinamiento de células B humanas P2RY8
Erick Lu1, Finn D Wolfreys1, Jagan R Muppidi1,2
1Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, CA, USA.
Nature
|March 8, 2019
Resumen
Los investigadores identificaron a S-geranilgeranil-L-glutatión (GGG) como un nuevo ligando para el receptor P2RY8, crucial para regular el confinamiento de las células B del centro germinal e implicado en tumores malignos de células B.
Área de la Ciencia:
- Inmunología y Biología del Cáncer
- Biología molecular y celular
Sus antecedentes:
- Los centros germinales son críticos para la inmunidad adaptativa, pero también están relacionados con los cánceres de células B.
- Los mecanismos que confinan las células B del centro germinal móvil dentro de los folículos no se comprenden completamente.
- El receptor P2RY8, involucrado en la migración y el crecimiento de las células B, suele mutar en los linfomas de células B.
Objetivo del estudio:
- Para identificar el ligando desconocido para el receptor P2RY8.
- Para aclarar el papel de la señalización P2RY8 en la organización del centro germinal y las células malignas B.
Principales métodos:
- Detección de ligandos P2RY8 en muestras biológicas y supernatantes celulares.
- Fraccionamiento bioquímico y espectrometría de masas para identificar nuevas biomoléculas.
- Ensayos funcionales que evalúan la migración celular, la señalización y la activación de los receptores in vitro e in vivo.
Principales resultados:
- El S-geranil-L-glutatión (GGG) fue identificado como un potente ligando P2RY8 presente en los tejidos linfoides.
- El GGG inhibió la migración mediada por quimiocinas de las células B del centro germinal y de las células auxiliares foliculares T.
- La gamma-glutamiltransferasa-5 (GGT5) metabolizó el GGG, y su sobreexpresión interrumpió el confinamiento de las células B mediado por P2RY8.
Conclusiones:
- GGG es una molécula de señalización intercelular que organiza las respuestas del centro germinal controlando la migración de las células B.
- GGT5 establece un gradiente GGG, regulando la localización de las células B dentro de los tejidos linfoides.
- La señalización GGG y P2RY8 puede representar objetivos terapéuticos para tumores malignos de células B y otros cánceres.
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