On the role of proteases, their inhibitors and the extracellular matrix in promoting neurite outgrowth.
Using a novel method, a monoclonal antibody was produced which can directly block the activity of an extracellular matrix-associated neurite outgrowth promoting complex (Matthew and Patterson, 1983). Presumably binding at or near the active site, this antibody recognizes a determinant consisting of heparan sulfate and a larger molecule which is likely to be laminin (Matthew et al., in preparation). The antibody has been further used to localize this determinant in adult tissues in vivo. Extracellular binding is seen at sites known to promote axon regeneration in the peripheral nervous system and is not seen in the central nervous system (Matthew et al., in preparation). In investigating how neurons may modify their environment as they grow processes, we have recently found that sensory and sympathetic neurons spontaneously release a collagenase and a plasminogen activator from their distal processes and/or growth cones (Pittman, 1985). A 43 kD irreversible inhibitor of the plasminogen activator is secreted by cardiac myocytes and is found on the surfaces of cultured neurons (Pittman, 1984). This inhibitor is also released by nonneuronal cell cultures from peripheral, but not central, nerves (Pittman, unpublished). Of interest in relation to the proteoglycan neurite outgrowth promoting complex is the finding that the 43 kD inhibitor preparation binds heparin tightly and can displace laminin from its heparin binding site (Patterson and Pittman, unpublished). Thus it is possible that the protease/inhibitor system could affect outgrowth via interaction with the neurite outgrowth promoting complex in the extracellular matrix.
P H
PH
Patterson
D000818:Animals; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D011508:Chondroitin Sulfate Proteoglycans / Q000502:physiology; D004727:Endothelium / Q000378:metabolism; D000939:Epitopes; D005109:Extracellular Matrix; D005347:Fibroblasts / Q000378:metabolism; D006023:Glycoproteins / Q000502:physiology; D006054:Goldfish; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000502:physiology; D006801:Humans; D007797:Laminin / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009475:Neurons, Afferent / Q000201:enzymology; D010447:Peptide Hydrolases / Q000502:physiology*; D011480:Protease Inhibitors / Q000502:physiology; D051381:Rats; D013564:Sympathetic Nervous System / Q000201:enzymology; D010959:Tissue Plasminogen Activator / Q000502:physiology
D000911:Antibodies, Monoclonal; D011508:Chondroitin Sulfate Proteoglycans; D000939:Epitopes; D006023:Glycoproteins; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D007797:Laminin; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D010447:Peptide Hydrolases; D011480:Protease Inhibitors; D010959:Tissue Plasminogen Activator