RGD Reference Report - Microanatomy of axon/glial signaling during Wallerian degeneration. - Rat Genome Database

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Microanatomy of axon/glial signaling during Wallerian degeneration.

Authors: Guertin, AD  Zhang, DP  Mak, KS  Alberta, JA  Kim, HA 
Citation: Guertin AD, etal., J Neurosci. 2005 Mar 30;25(13):3478-87.
RGD ID: 1582139
Pubmed: PMID:15800203   (View Abstract at PubMed)
PMCID: PMC6724908   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.3766-04.2005   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to axon injury  IDA 1582139 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
lateral loop  IDA 1582139 RGD 
microvillus  IDA 1582139 RGD 
perinuclear region of cytoplasm  IDA 1582139 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Erbb2  (erb-b2 receptor tyrosine kinase 2)

Additional Information