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

被引:49
作者
Esapa, CT
Bentham, GRB
Schröder, JE
Kröger, S
Blake, DJ
机构
[1] Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England
[2] Univ Mainz, Inst Physiol Chem, Mainz, Germany
基金
英国惠康基金;
关键词
dystroglycan; processing; mucin; glycosylation; proteasome inhibitor;
D O I
10.1016/S0014-5793(03)01230-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
引用
收藏
页码:209 / 216
页数:8
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