Fig. 1

Dystroglycan gene structure, biosynthesis and intracellular transport. DG is encoded by the DAG1 gene, which is composed of six exons and five introns, and is transcribed into a single mRNA. The encoded polypeptide undergoes post-translational cleavage in the endoplasmic reticulum (ER) in an autocatalytic fashion to yield two subunits, α-DG and β-DG. Then O-mannosyl glycans are added to the mucin-like region of α-DG in the ER and Golgi complex, and the two subunits are targeted to the plasma membrane, where they remain non-covalently bound. Upon cell-ECM interaction the β-DG subunit becomes phosphorylated, allowing its dissociation from α-DG and its retrograde targeting to the ER and the nucleus, where it modulates nuclear structure and activity, including the expression of genes involved in normal cell proliferation. Created with BioRender.com