Nna1 mediates Purkinje cell dendritic development via lysyl oxidase propeptide and NF-κB signaling. Academic Article uri icon

Overview

abstract

  • The molecular pathways controlling cerebellar Purkinje cell dendrite formation and maturation are poorly understood. The Purkinje cell degeneration (pcd) mutant mouse is characterized by mutations in Nna1, a gene discovered in an axonal regenerative context, but whose actual function in development and disease is unknown. We found abnormal development of Purkinje cell dendrites in postnatal pcd(Sid) mice and linked this deficit to a deletion mutation in exon 7 of Nna1. With single cell gene profiling and virus-based gene transfer, we analyzed a molecular pathway downstream to Nna1 underlying abnormal Purkinje cell dendritogenesis in pcd(Sid) mice. We discovered that mutant Nna1 dramatically increases intranuclear localization of lysyl oxidase propeptide, which interferes with NF-κB RelA signaling and microtubule-associated protein regulation of microtubule stability, leading to underdevelopment of Purkinje cell dendrites. These findings provide insight into Nna1's role in neuronal development and why its absence renders Purkinje cells more vulnerable.

publication date

  • October 6, 2010

Research

keywords

  • Dendrites
  • GTP-Binding Proteins
  • NF-kappa B
  • Protein-Lysine 6-Oxidase
  • Purkinje Cells
  • Serine-Type D-Ala-D-Ala Carboxypeptidase
  • Signal Transduction

Identity

PubMed Central ID

  • PMC4457472

Scopus Document Identifier

  • 77957310202

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2010.08.013

PubMed ID

  • 20920790

Additional Document Info

volume

  • 68

issue

  • 1