Journal article
Mammalian O-mannosylation of cadherins and plexins is independent of protein O-mannosyltransferases 1 and 2
From the1
the2
Zuckerman Mind Brain Behavior Institute, Department of Systems Biology, and3
Howard Hughes Medical Institute Columbia University, New York, New York 100324
Protein O-mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans.
Deficiencies in enzymes catalyzing O-Man biosynthesis, including the two human protein O-mannosyltransferases, POMT1 and POMT2, underlie a subgroup of congenital muscular dystrophies designated α-dystroglycanopathies, because deficient O-Man glycosylation of α-dystroglycan disrupts laminin interaction with α-dystroglycan and the extracellular matrix.
To explore the functions of O-Man glycans on cadherins and protocadherins, we used a combinatorial gene-editing strategy in multiple cell lines to evaluate the role of the two POMTs initiating O-Man glycosylation and the major enzyme elongating O-Man glycans, the protein O-mannose β-1,2-N-acetylglucosaminyltransferase, POMGnT1.
Surprisingly, O-mannosylation of cadherins and protocadherins does not require POMT1 and/or POMT2 in contrast to α-dystroglycan, and moreover, the O-Man glycans on cadherins are not elongated. Thus, the classical and evolutionarily conserved POMT O-mannosylation pathway is essentially dedicated to α-dystroglycan and a few other proteins, whereas a novel O-mannosylation process in mammalian cells is predicted to serve the large cadherin superfamily and other proteins.
Language: | Undetermined |
---|---|
Publisher: | American Society for Biochemistry and Molecular Biology |
Year: | 2017 |
Pages: | 11586-11598 |
ISSN: | 1083351x , 00219258 and 10678816 |
Types: | Journal article |
DOI: | 10.1074/jbc.M117.794487 |
ORCIDs: | Narimatsu, Yoshiki , Joshi, Hiren Jitendra , Clausen, Henrik and Halim, Adnan |