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On the role of proteases, their inhibitors and the extracellular matrix in promoting neurite outgrowth

Patterson, Paul H. (1985) On the role of proteases, their inhibitors and the extracellular matrix in promoting neurite outgrowth. Journal de Physiologie, 80 (4). pp. 207-211. ISSN 0021-7948.

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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 This inhibitor is also released by nonneuronal cell cultures from peripheral, but not central, nerves (Pittman, unpublished).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preparation binds heparin tightly and can displace laminin from its heparin binding site (Patterson and Pittman, unpublished).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.

Item Type:Article
Additional Information:© 1985 Masson, Paris. Received 11 January 1985. This work was supported by the NINCDS, the Jane Coffin Childs Memorial Fund, Rita Allen and McKnight Foundations, and the Muscular Dystrophy Association. In addition to those named, the following colleagues contributed to the data presented in this article: A. Chiu, J. Carnahan, D. McDowell, V. Yee, E. Silvestro and M. Ryder.
Funding AgencyGrant Number
National Institute of Neurological and Communicative Disorders and Stroke (NINCDS)UNSPECIFIED
Jane Coffin Childs Memorial Fund for Medical ResearchUNSPECIFIED
Rita Allen FoundationUNSPECIFIED
McKnight FoundationUNSPECIFIED
Muscular Dystrophy AssociationUNSPECIFIED
Subject Keywords:laminin; heparan sulfate; plasminogen activator; protease; neurite outgrowth; axon regeneration; proteoglycan
Issue or Number:4
Record Number:CaltechAUTHORS:20151229-145353509
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:63251
Deposited By: George Porter
Deposited On:24 Feb 2016 20:47
Last Modified:03 Oct 2019 09:26

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