title: The developmentally regulated expression of Menkes protein ATP7A suggests a role in axon extension and synaptogenesis.
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 exhibits axonal localization. These results support a role for ATP7A in axon extension, which may contribute to the severe neurodegeneration characteristic of MD.
authors.affiliation: Department of Neuroscience, University of Connecticut Health Center, Farmington, Conn., USA.
authors.forename: Rajaâ
authors.initials: R
authors.lastname: El Meskini
authors.forename: Laura B
authors.initials: LB
authors.lastname: Cline
authors.forename: Betty A
authors.initials: BA
authors.lastname: Eipper
authors.forename: Gabriele V
authors.initials: GV
authors.lastname: Ronnett
mesh_terms: D000251:Adenosine Triphosphatases / Q000096:biosynthesis*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D019771:Axotomy; D015153:Blotting, Western; D027682:Cation Transport Proteins / Q000096:biosynthesis*; D000073840:Copper-Transporting ATPases; D004622:Embryo, Mammalian; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009416:Nerve Regeneration / Q000502:physiology; D009474:Neurons / Q000166:cytology; D009830:Olfactory Bulb / Q000254:growth & development* / Q000378:metabolism; D009831:Olfactory Mucosa / Q000254:growth & development* / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000502:physiology*
chemical_list: C486201:Atp7a protein, mouse; D027682:Cation Transport Proteins; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases