α-dystroglycan is a cell surface receptor that is expressed in many tissues including the nervous system. The study shows that a recombinant, non-glycosylated N-terminal fragment of α-dystroglycan comprising residues 30 to 315 [αDG (30-315)] bound to laminin-2/-4 and laminin-1, fibronectin and fibrinogen, all molecules highly upregulated in the regenerating peripheral nerve. The interaction was concentration dependent and saturable and could not be inhibited by heparin suggesting only minor involvement of sulfated carbohydrate moieties. In contrast to published data, addition of bivalent cations increased the binding affinity by only ten fold. αDG (30-315) promotes neurite extension of PC12 cells in a similar amount as described for laminin isoforms and could be inhibited in a concentration dependent manner by αDG (30-315) itself, soluble laminin-1, partially by heparin, EDTA, and an RGD-peptide. Furthermore, co-immunoprecipitations between α-dystroglycan and β1-integrin from PC12 cell surfaces suggested complex interactions between neuronal dystroglycan, integrins, and the ECM that induce neurite extension in vitro.
ASJC Scopus subject areas
- Molecular Biology
- Cellular and Molecular Neuroscience
- Cell Biology