The Lecticans of Mammalian Brain Perineural Net Are O‑Mannosylated

O-Mannosylation
is an important protein modification in brain. During the last years,
a few mammalian proteins have been identified as targets of the protein-O-mannosyltransferases 1 and 2. However, these still cannot
explain the high content of O-mannosyl glycans in brain and the strong
brain involvement of congenital muscular dystrophies caused by POMT
mutations (Walker-Warburg syndrome, dystroglycanopathies). By fractionating
and analyzing the glycoproteome of mouse and calf brain lysates, we
could show that proteins of the perineural net, the lecticans, are
O-mannosylated, indicating that major components of neuronal extracellular
matrix are O-mannosylated in mammalian brain. This finding corresponds
with the high content of O-mannosyl glycans in brain
as well as with the brain involvement of dystroglycanopathies. In
contrast, the lectican neurocan is not O-mannosylated when recombinantly
expressed in EBNA-293 cells, revealing the possibility of different
control mechanisms for the initiation of O-mannosylation in different
cell types.