Document Detail


Microanatomy of axon/glial signaling during Wallerian degeneration.
MedLine Citation:
PMID:  15800203     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
How do myelinated axons signal to the nuclei of cells that enwrap them? The cell bodies of oligodendrocytes and Schwann cells are segregated from axons by multiple layers of bimolecular lipid leaflet and myelin proteins. Conventional signal transduction strategies would seem inadequate to the challenge without special adaptations. Wallerian degeneration provides a model to study axon-to-Schwann cell signaling in the context of nerve injury. We show a hitherto undetected rapid, but transient, activation of the receptor tyrosine kinase erbB2 in myelinating Schwann cells after sciatic nerve axotomy. Deconvolving microscopy using phosphorylation state-specific antibodies shows that erbB2 activation emanates from within the microvilli of Schwann cells, in direct contact with the axons they enwrap. To define the functional role of this transient activation, we used a small molecule antagonist of erbB2 activation (PKI166). The response of myelinating Schwann cells to axotomy is inhibited by PKI166 in vivo. Using neuron/Schwann cell cocultures prepared in compartmentalized cell culture chambers, we show that even transient activation of erbB2 is sufficient to initiate Schwann cell demyelination and that the initiating functions of erbB2 are localized to Schwann cells.
Authors:
Amy D Guertin; Dan P Zhang; Kimberley S Mak; John A Alberta; Haesun A Kim
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  25     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-03-31     Completed Date:  2006-03-23     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3478-87     Citation Subset:  IM    
Affiliation:
Department of Biological Sciences, Rutgers University, Newark, New Jersey 07102, USA.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Axotomy / methods
Blotting, Western / methods
Bromodeoxyuridine / metabolism
Cell Proliferation
Cells, Cultured
Coculture Techniques / methods
Demyelinating Diseases / chemically induced,  metabolism,  pathology
Disease Models, Animal
Embryo, Mammalian
Female
Fluorescent Antibody Technique / methods
Ganglia, Spinal / pathology
Gene Expression / drug effects,  physiology
Glycoproteins / metabolism
Immunoprecipitation / methods
Mitogen-Activated Protein Kinase Kinases / metabolism
Myelin Basic Proteins / metabolism
Myelin Sheath / metabolism,  pathology
Neuregulins / pharmacology
Neuroglia / drug effects,  physiology*
Neurons / drug effects,  physiology*
Platelet-Derived Growth Factor / pharmacology
Pyrimidines / administration & dosage
Pyrroles / administration & dosage
Rats
Rats, Sprague-Dawley
Receptor Protein-Tyrosine Kinases / metabolism
Schwann Cells / pathology
Sciatic Neuropathy / pathology
Signal Transduction / drug effects,  physiology*
Sodium Channels / metabolism
Time Factors
Wallerian Degeneration / pathology*,  physiopathology
Grant Support
ID/Acronym/Agency:
R01-NS45939-01/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Erbb2 protein, rat; 0/Glycoproteins; 0/Myelin Basic Proteins; 0/Neuregulins; 0/PKI 166; 0/Platelet-Derived Growth Factor; 0/Pyrimidines; 0/Pyrroles; 0/Sodium Channels; 59-14-3/Bromodeoxyuridine; EC 2.7.10.1/Receptor Protein-Tyrosine Kinases; EC 2.7.12.2/Mitogen-Activated Protein Kinase Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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