Disruption of axo-glial junctions causes cytoskeletal disorganization and degeneration of Purkinje neuron axons

German P. Garcia-Fresco, Aurea D. Sousa, Anilkumar M. Pillai, Sheryl S. Moy, Jacqueline Crawley, Lino Tessarollo, Jeffrey L. Dupree, Manzoor A. Bhat

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Axo-glial junctions (AGJs) play a critical role in the organization and maintenance of molecular domains in myelinated axons. Neurexin IV/Caspr1/paranodin (NCP1) is an important player in the formation of AGJs because it recruits a paranodal complex implicated in the tethering of glial proteins to the axonal membrane and cytoskeleton. Mice deficient in either the axonal protein NCP1 or the glial ceramide galactosyltransferase (CGT) display disruptions in AGJs and severe ataxia. In this article, we correlate these two phenotypes and show that both NCP1 and CGT mutants develop large swellings accompanied by cytoskeletal disorganization and degeneration in the axons of cerebellar Purkinje neurons. We also show that all spectrin is part of the paranodal complex and that, although not properly targeted, this complex is still formed in CGT mutants. Together, these findings establish a physiologically relevant link between AGJs and axonal cytoskeleton and raise the possibility that some neurodegenerative disorders arise from disruption of the AGJs.

Original languageEnglish (US)
Pages (from-to)5137-5142
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number13
DOIs
StatePublished - Mar 28 2006
Externally publishedYes

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Keywords

  • Ataxia
  • Cerebellum
  • Myelin
  • Paranodes

ASJC Scopus subject areas

  • Genetics
  • General

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