N-terminal alpha-dystroglycan binds to different extracellular matrix molecules expressed in regenerating peripheral nerves in a protein-mediated manner and promotes neurite extension of PC12 cells.
alpha-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 alpha-dystroglycan comprising residues 30 to 315 [alphaDG (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.alphaDG (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 alphaDG (30-315) itself, soluble laminin-1, partially by heparin, EDTA, and an RGD-peptide. Furthermore, co-immunoprecipitations between alpha-dystroglycan and beta1-integrin from PC12 cell surfaces suggested complex interactions between neuronal dystroglycan, integrins, and the ECM that induce neurite extension in vitro.
Hall
Heike
H
Institute for Biomedical Engineering and Department of Material Sciences, ETH and University of Zurich, Zurich, Switzerland. heike.hall@mat.ethz.ch
Bozic
Damir
D
Michel
Kathrin
K
Hubbell
Jeffrey A
JA
D000818:Animals; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D049030:Dystroglycans; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D016501:Neurites / Q000378:metabolism*; D016716:PC12 Cells; D010525:Peripheral Nerves / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D051381:Rats
D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D008562:Membrane Glycoproteins; D049030:Dystroglycans