High degree of conservation of the enzymes synthesizing the laminin-binding glycoepitope of α-dystroglycan

• Main Authors: Maria Giulia Bigotti, Andrea Brancaccio
• Format: Article
• Language: English
• Published: The Royal Society 2021-09-01
• Series: Open Biology
• Subjects: dystroglycan; post-translational glycosylation; M3 core structure; laminin-binding glycoepitope; glycosyltransferases; protein evolution
• Online Access: https://royalsocietypublishing.org/doi/10.1098/rsob.210104

The dystroglycan (DG) complex plays a pivotal role for the stabilization of muscles in Metazoa. It is formed by two subunits, extracellular α-DG and transmembrane β-DG, originating from a unique precursor via a complex post-translational maturation process. The α-DG subunit is extensively glycosylated in sequential steps by several specific enzymes and employs such glycan scaffold to tightly bind basement membrane molecules. Mutations of several of these enzymes cause an alteration of the carbohydrate structure of α-DG, resulting in severe neuromuscular disorders collectively named dystroglycanopathies. Given the fundamental role played by DG in muscle stability, it is biochemically and clinically relevant to investigate these post-translational modifying enzymes from an evolutionary perspective. A first phylogenetic history of the thirteen enzymes involved in the fabrication of the so-called ‘M3 core’ laminin-binding epitope has been traced by an overall sequence comparison approach, and interesting details on the primordial enzyme set have emerged, as well as substantial conservation in Metazoa. The optimization along with the evolution of a well-conserved enzymatic set responsible for the glycosylation of α-DG indicate the importance of the glycosylation shell in modulating the connection between sarcolemma and surrounding basement membranes to increase skeletal muscle stability, and eventually support movement and locomotion.