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The effects of post‐translational processing on dystroglycan synthesis and trafficking 1
Author(s) -
Esapa Chris T.,
Bentham Graham R.B.,
Schröder Jörn E.,
Kröger Stephan,
Blake Derek J.
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(03)01230-4
Subject(s) - dystroglycan , glycosylation , cleavage (geology) , microbiology and biotechnology , n linked glycosylation , chemistry , proteolysis , mutant , glycoprotein , biochemistry , biology , cell , laminin , gene , glycan , enzyme , paleontology , fracture (geology)
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.