The effects of post‐translational processing on dystroglycan synthesis and trafficking

FEBS Letters

Schröder, Jörn E.¹  Kröger, Stephan¹  Esapa, Chris T.²  Bentham, Graham R.B.²  Blake, Derek J.² 

[1] Institute for Physiological Chemistry, University of Mainz, Mainz, Germany;Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK

关键词: Dystroglycan;    Processing;    Mucin;    Glycosylation;    Proteasome inhibitor;   

DOI  :  10.1016/S0014-5793(03)01230-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Dystroglycan is a component of the dystrophin glycoprotein complex that is cleaved into two polypeptides by an unidentified protease. To determine the role of post-translational processing on dystroglycan synthesis and trafficking we expressed the dystroglycan precursor and mutants thereof in a heterologous system. A point mutant in the processing site, S655A, prevented proteolytic cleavage but had no effect upon the surface localisation of dystroglycan. Mutation of two N-linked glycosylation sites that flank the cleavage site inhibited proteolytic processing of the precursor. Furthermore, chemical inhibition of N- and O-linked glycosylation interfered with the processing of the precursor and reduced the levels of dystroglycan at the cell surface. Dystroglycan processing was also inhibited by the proteasome inhibitor lactacystin. N-linked glycosylation is a prerequisite for efficient proteolytic processing and cleavage and glycosylation are dispensable for cell surface targeting of dystroglycan.

【 授权许可】

Unknown