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

70 Citations (Scopus)

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

Fingerprint

Purkinje Cells
Neuroglia
Axons
N-Acylsphingosine Galactosyltransferase
Cytoskeleton
Spectrin
Ataxia
Neurodegenerative Diseases
Proteins
Maintenance
Phenotype
Membranes

Keywords

  • Ataxia
  • Cerebellum
  • Myelin
  • Paranodes

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Disruption of axo-glial junctions causes cytoskeletal disorganization and degeneration of Purkinje neuron axons. / Garcia-Fresco, German P.; Sousa, Aurea D.; Pillai, Anilkumar M.; Moy, Sheryl S.; Crawley, Jacqueline; Tessarollo, Lino; Dupree, Jeffrey L.; Bhat, Manzoor A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 13, 28.03.2006, p. 5137-5142.

Research output: Contribution to journalArticle

Garcia-Fresco, German P. ; Sousa, Aurea D. ; Pillai, Anilkumar M. ; Moy, Sheryl S. ; Crawley, Jacqueline ; Tessarollo, Lino ; Dupree, Jeffrey L. ; Bhat, Manzoor A. / Disruption of axo-glial junctions causes cytoskeletal disorganization and degeneration of Purkinje neuron axons. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 13. pp. 5137-5142.
@article{0c9919163056465da531aaad89e617b6,
title = "Disruption of axo-glial junctions causes cytoskeletal disorganization and degeneration of Purkinje neuron axons",
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.",
keywords = "Ataxia, Cerebellum, Myelin, Paranodes",
author = "Garcia-Fresco, {German P.} and Sousa, {Aurea D.} and Pillai, {Anilkumar M.} and Moy, {Sheryl S.} and Jacqueline Crawley and Lino Tessarollo and Dupree, {Jeffrey L.} and Bhat, {Manzoor A.}",
year = "2006",
month = "3",
day = "28",
doi = "10.1073/pnas.0601082103",
language = "English (US)",
volume = "103",
pages = "5137--5142",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "13",

}

TY - JOUR

T1 - Disruption of axo-glial junctions causes cytoskeletal disorganization and degeneration of Purkinje neuron axons

AU - Garcia-Fresco, German P.

AU - Sousa, Aurea D.

AU - Pillai, Anilkumar M.

AU - Moy, Sheryl S.

AU - Crawley, Jacqueline

AU - Tessarollo, Lino

AU - Dupree, Jeffrey L.

AU - Bhat, Manzoor A.

PY - 2006/3/28

Y1 - 2006/3/28

N2 - 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.

AB - 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.

KW - Ataxia

KW - Cerebellum

KW - Myelin

KW - Paranodes

UR - http://www.scopus.com/inward/record.url?scp=33645242299&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645242299&partnerID=8YFLogxK

U2 - 10.1073/pnas.0601082103

DO - 10.1073/pnas.0601082103

M3 - Article

C2 - 16551741

AN - SCOPUS:33645242299

VL - 103

SP - 5137

EP - 5142

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 13

ER -