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PMID: 7540614 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

ARIA can be released from extracellular matrix through cleavage of a heparin-binding domain.

The Journal of cell biology ·Vol. 130 ·No. 1 ·1995-07-00 ·Pages 127-35

Loeb JA, Fischbach GD

Abstract

ARIA, or acetylcholine receptor-inducing activity, is a polypeptide that stimulates the synthesis of acetylcholine receptors in skeletal muscle. Here we demonstrate that the ability of ARIA to induce phosphorylation of its receptor in muscle is blocked by highly charged glycosaminoglycans. ARIA constructs lacking the NH2-terminal portion, containing an immunoglobulin-like domain, are fully active and are not inhibited by glycosaminoglycans. Limited proteolysis of ARIA with subtilisin blocks the glycosaminoglycan interaction by degrading this NH2-terminal portion, but preserves the active, EGF-like domain. We also show that ARIA can be released from freshly dissociated cells from embryonic chick spinal cord and cerebellum by either heparin, high salt or limited proteolysis with subtilisin, suggesting that ARIA is bound to the extracellular matrix through charged interactions. We present a model of how ARIA may be stored in extracellular matrix at developing synapses and how its release may be mediated by local proteolysis.

MeSH Terms
Amino Acid Sequence Animals Avian Proteins Cerebellum/chemistry Chick Embryo Extracellular Matrix/chemistry,metabolism Heparin/metabolism,pharmacology Molecular Sequence Data Nerve Tissue Proteins/metabolism Neuregulin-1 Phosphorylation Phosphotyrosine Receptors, Cell Surface/metabolism Receptors, Nicotinic/metabolism Recombinant Proteins Spinal Cord/chemistry Synapses/metabolism Tyrosine/analogs & derivatives,metabolism
Chemicals
Avian Proteins NRG1 protein, Gallus gallus Nerve Tissue Proteins Neuregulin-1 Receptors, Cell Surface Receptors, Nicotinic Recombinant Proteins Phosphotyrosine Tyrosine Heparin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Loeb J A
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Fischbach G D
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.130.1.127
Published
1995-07-00
Pages
127-35
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2120519
Subset
IM
Grants
NINDS NIH HHS · K08 NS01659-02 · United States
NINDS NIH HHS · NS18458 · United States
External Links
PubMed source DOI: 10.1083/jcb.130.1.127 PMC Full Text View journal details
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