Neuron Glia Biology



Article

Disrupted axo-glial junctions result in accumulation of abnormal mitochondria at nodes of Ranvier


STEVEN EINHEBER a1c1, MANZOOR A. BHAT a2a3a4a5 and JAMES L. SALZER a6a7a8
a1 Hunter College School of Health Sciences, New York, USA
a2 Curriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, USA
a3 Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, USA
a4 Neurodevelopmental Disorders Research Center, University of North Carolina School of Medicine, Chapel Hill, USA
a5 Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, USA
a6 Department of Cell Biology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, USA
a7 Department of Neurology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, USA
a8 Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, USA

Article author query
einheber s   [PubMed][Google Scholar] 
bhat ma   [PubMed][Google Scholar] 
salzer jl   [PubMed][Google Scholar] 

Abstract

Mitochondria and other membranous organelles are frequently enriched in the nodes and paranodes of peripheral myelinated axons, particularly of large caliber axons. The physiological role(s) of this organelle enrichment and the rheologic factors that regulate it are not well understood. Previous studies indicate that axonal transport of organelles across the nodal/paranodal region is regulated locally. In this study, we have examined the ultrastructure of myelinated axons in the sciatic nerves of mice deficient in contactin-associated protein (Caspr), an integral junctional component. These mice, which lack the normal septate-like junctions that promote attachment of the glial (paranodal) loops to the axon, contain aberrant mitochondria in their nodal/paranodal regions. Typically, these mitochondria are large, swollen and occupy prominent varicosities of the nodal axolemma. In contrast, mitochondria outside the nodal/paranodal regions of the myelinated axons appear normal. These findings suggest that paranodal junctions regulate mitochondrial transport and function in the axoplasm of the nodal/paranodal region of myelinated axons of peripheral nerves. They further indicate that paranodal junctions might have a role, either direct or indirect, in the local regulation of energy metabolism in the nodal region.

(Published Online March 5 2007)


Key Words: Contactin associated protein; Caspr; paranode; myelin; sciatic nerve; axonal transport.

Correspondence:
c1 Hunter College, School of Health Sciences, 425 E 25th Street, New York, NY 10010, USA, phone: 212 481 4502, email: seinhebe@hunter.cuny.edu