RGD Reference Report - M2 muscarinic receptor activation regulates Schwann cell differentiation and myelin organization. - Rat Genome Database

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M2 muscarinic receptor activation regulates Schwann cell differentiation and myelin organization.

Authors: Uggenti, Carolina  De Stefano, M Egle  Costantino, Michele  Loreti, Simona  Pisano, Annalinda  Avallone, Bice  Talora, Claudio  Magnaghi, Valerio  Tata, Ada Maria 
Citation: Uggenti C, etal., Dev Neurobiol. 2014 Jul;74(7):676-91. doi: 10.1002/dneu.22161. Epub 2014 Jan 9.
RGD ID: 12879828
Pubmed: PMID:24403178   (View Abstract at PubMed)
DOI: DOI:10.1002/dneu.22161   (Journal Full-text)

Glial cells express acetylcholine receptors. In particular, rat Schwann cells express different muscarinic receptor subtypes, the most abundant of which is the M2 subtype. M2 receptor activation causes a reversible arrest of the cell cycle. This negative effect on Schwann cell proliferation suggests that these cells may possibly progress into a differentiating program. In this study we analyzed the in vitro modulation, by the M2 agonist arecaidine, of transcription factors and specific signaling pathways involved in Schwann cell differentiation. The arecaidine-induced M2 receptor activation significantly upregulates transcription factors involved in the promyelinating phase (e.g., Sox10 and Krox20) and downregulates proteins involved in the maintenance of the undifferentiated state (e.g., c-jun, Notch-1, and Jagged-1). Furthermore, arecaidine stimulation significantly increases the expression of myelin proteins, which is accompanied by evident changes in cell morphology, as indicated by electron microscopy analysis, and by substantial cellular re-distribution of actin and cell adhesion molecules. Moreover, ultrastructural and morphometric analyses on sciatic nerves of M2/M4 knockout mice show numerous degenerating axons and clear alterations in myelin organization compared with wild-type mice. Therefore, our data demonstrate that acetylcholine mediates axon-glia cross talk, favoring Schwann cell progression into a differentiated myelinating phenotype and contributing to compact myelin organization.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Sox10Ratcellular response to xenobiotic stimulus  IEP arecaidineRGD 

Objects Annotated

Genes (Rattus norvegicus)
Sox10  (SRY-box transcription factor 10)


Additional Information