No effect of genetic deletion of contactin-associated protein (CASPR) on axonal orientation and synaptic plasticity

Anilkumar M. Pillai, German P. Garcia-Fresco, Aurea D. Sousa, Jeffrey L. Dupree, Benjamin D. Philpot, Manzoor A. Bhat

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Myelinated axons are endowed with a specialized domain structure that is essential for saltatory action potential conduction. The paranodal domain contains the axoglial junctions and displays a unique ultrastructure that resembles the invertebrate septate junctions (SJs). Biochemical characterizations of the paranodal axoglial SJs have identified several molecular components that include Caspr and contactin (Cont) on the axonal side and neurofascin 155 kDa (NF155) isoform on the glial side. All these proteins are essential for the formation of the axoglial SJs. Based on the interactions between Caspr and Cont and their colocalization in the CA1 synaptic areas, it was proposed that the synaptic function of Cont requires Caspr. Here we have extended the phenotypic analysis of CASPR mutants to address further the role of Caspr at the axoglial SJs and also in axonal orientation and synaptic plasticity. We report that, in CASPR mutants, the smooth endoplasmic reticulum (SER) forms elongated membranous complexes that accumulate at the nodal/ paranodal region and stretch into the juxtaparanodal region, a defect that is consistent with the paranodal disorganization. We show that the cerebellar microorganization is unaffected in CASPR mutants. We also demonstrate that Caspr function is not essential for normal CA1 synaptic transmission and plasticity. Taken together with previous findings, our results highlight that the Caspr/ Cont complex is essential for the formation of axoglial SJs, whereas Cont may regulate axonal orientation and synaptic plasticity independent of its association with Caspr.

Original languageEnglish (US)
Pages (from-to)2318-2331
Number of pages14
JournalJournal of Neuroscience Research
Volume85
Issue number11
DOIs
StatePublished - Aug 15 2007

Keywords

  • Axoglial junctions
  • Cerebellum
  • Cytoskeleton
  • Hippocampus
  • Myelin
  • Paranodes
  • Purkinje neurons

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'No effect of genetic deletion of contactin-associated protein (CASPR) on axonal orientation and synaptic plasticity'. Together they form a unique fingerprint.

Cite this