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SGK196 es una O-manosa quinasa específica para la glicosilación requerida para la función de los distroglicanos
Takako Yoshida-Moriguchi1, Tobias Willer, Mary E Anderson
1Howard Hughes Medical Institute, Department of Molecular Physiology and Biophysics, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242-1101, USA.
Science (New York, N.Y.)
|August 10, 2013
Resumen
Los investigadores identificaron las enzimas clave GTDC2 y B3GALNT2, y la quinasa SGK196, responsables de producir una estructura de azúcar crucial para la función de los distroglicanos. Las mutaciones en estos genes causan distrofia muscular congénita.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Biología celular Biología celular.
Sus antecedentes:
- La unión del distroglicano a las proteínas del dominio laminina-G requiere un trisacárido O-mannosil fosforilado específico.
- Las enzimas responsables de sintetizar esta estructura crítica de glicano no se comprendieron completamente.
Objetivo del estudio:
- Para dilucidar la vía enzimática para la síntesis del O-mannosil trisacárido fosforilado.
- Identificar las enzimas involucradas en la glicosilación de los distroglicanos y su papel en la distrofia muscular congénita.
Principales métodos:
- Pruebas enzimáticas para caracterizar la actividad de la glucosiltransferasa.
- Identificación de la actividad de la quinasa a través del análisis bioquímico.
- Análisis de mutaciones genéticas en relación con la función de las proteínas.
Principales resultados:
- Glycosyltransferase-like domain-containing 2 (GTDC2) actúa como una manosa β 1,4-N-acetilglucosaminyltransferasa ligada a la proteína O.
- La β 1,3-N-acetilgalactosaminiltransferasa2 (B3GALNT2) extiende el producto GTDC2 para formar el O-mannosil trisacárido.
- SGK196 fue identificado como una quinasa atípica que fosforila el residuo de O-manosa después de la acción de GTDC2 y B3GALNT2.
Conclusiones:
- El estudio identifica a GTDC2, B3GALNT2 y SGK196 como enzimas clave en la síntesis del glicano que se une al distroglicano.
- Las mutaciones en estos genes interrumpen la función de los distroglicanos, lo que lleva a la distrofia muscular congénita.
- Esto proporciona una visión de los mecanismos moleculares subyacentes a ciertas formas de distrofia muscular.
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