Human O-Mannosylation independent of POMT1/2

Protein O-mannosylation is found in yeast and metazoans and a family of conserved orthologous polypeptide O-mannosyltransferases is believed to initiate this important posttranslational modification. We recently discovered that the large families of cadherins and protocadherins carry highly conserved O-Man glycans in specific EC domains, and it was suggested that the function of E-Cadherin was dependent on the O-Man glycans. Deficiencies in the two human polypeptide O-mannosyltransferases, POMT1 and T2, underlie a subgroup of congenital muscular dystrophies (CMD) designated α-dystroglycanopathies, because deficient O-Man glycans on -dystroglycan impair laminin interaction with -dystroglycan and the dystrophin complex. In order 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 to the role of the two POMTs initiation O-Man glycosylation and the major enzyme elongating O-Man glycans, the POMGNT1 2GlcNAc-transferase. Surprisingly, we discovered that O-Man glycans on cadherins and protocadherins do not appear to require POMT1 and T2 and moreover that the O-Man glycans on these proteins are not elongated in contrast to those on dystroglycan.