The developmentally regulated expression of Menkes protein ATP7A suggests a role in axon extension and synaptogenesis

Rajaâ El Meskini, Laura B. Cline, Betty A. Eipper, Gabriele V. Ronnett

Research output: Contribution to journalArticlepeer-review

Abstract

Menkes disease (MD) is a neurodegenerative disorder caused by mutation of the copper transporter ATP7A. While several enzymes expressed in mature neurons require copper, MD neurodegenerative changes cannot be explained by known requirements for ATP7A in neuronal development. To investigate additional roles for ATP7A during development, we characterized its pattern of expression using the olfactory system as a neurodevelopmental model. ATP7A expression in neurons was developmentally regulated rather than constitutively. Initially expressed in the cell bodies of developing neurons, ATP7A protein later shifted to extending axons, peaking prior to synaptogenesis. Similarly, after injury-stimulated neurogenesis, ATP7A expression increased in neurons and axons preceding synaptogenesis. Interestingly, copper-transport-deficient ATP7A still exhibitsaxonal localization. These results support a role for ATP7A in axon extension, which may contribute to the severe neurodegeneration characteristic of MD.

Original languageEnglish (US)
Pages (from-to)333-348
Number of pages16
JournalDevelopmental Neuroscience
Volume27
Issue number5
DOIs
StatePublished - 2005

Keywords

  • ATP7A
  • Menkes disease
  • Neurodevelopment
  • Olfactory receptor neurons
  • Olfactory system
  • Process outgrowth
  • Regeneration
  • Synaptogenesis

ASJC Scopus subject areas

  • Neuroscience(all)

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