N-terminal α-dystroglycan binds to different extracellular matrix molecules expressed in regenerating peripheral nerves in a protein-mediated manner and promotes neurite extension of PC12 cells

Heike Hall, Damir Bozic, Kathrin Michel, Jeffrey A. Hubbell

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1062-1073
Number of pages12
JournalMolecular and Cellular Neuroscience
Volume24
Issue number4
DOIs
StatePublished - Dec 1 2003
Externally publishedYes

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Dystroglycans
PC12 Cells
Neurites
Peripheral Nerves
Extracellular Matrix
Laminin
Integrins
Heparin
Proteins
Cell Surface Receptors
Fibronectins
Immunoprecipitation
Edetic Acid
Fibrinogen
Nervous System
Cations
Protein Isoforms
Carbohydrates
laminin 1

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience

Cite this

N-terminal α-dystroglycan binds to different extracellular matrix molecules expressed in regenerating peripheral nerves in a protein-mediated manner and promotes neurite extension of PC12 cells. / Hall, Heike; Bozic, Damir; Michel, Kathrin; Hubbell, Jeffrey A.

In: Molecular and Cellular Neuroscience, Vol. 24, No. 4, 01.12.2003, p. 1062-1073.

Research output: Contribution to journalArticle

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