Whoa man! Unexpected protein O-mannosylation pathways in mammals

Abstract

The recent expansion of well-characterized O-mannosylated mammalian proteins beyond the archetypical example of α-dystroglycan has inspired new interest in the possibility of additional functional roles of this modification. In an effort to explore those roles, a new study now serendipitously uncovers the existence of an alternative pathway to the well-described POMT (protein O-mannosyltransferase) family of O-mannosyltransferases.

Figure 1.

Summary of the evolving O-mannosylation pathways. Left, the classical POMT1/POMT2-dependent O-mannosylation of α-DG. The classical pathway diverges with the activity of either POMGNT1 or POMGNT2 generating various core structures. Nucleocytoplasmic O-mannosylation (center) has also recently been described in yeast (10). Larsen and colleagues (8) describe the identification of POMT1/POMT2-independent O-mannosylation of proteins other than α-DG (right) that appear to not be extended but warrant further investigation. Green circles represent α-linked O-mannose attached to Ser or Thr residues on proteins, and blue squares represent N-acetylglucosamine with the linkage indicated.