title: Deglycosylation and subcellular redistribution of VMAT2 in the mesostriatal system during normal aging.
abstract: The vesicular monoamine transporter type 2 (VMAT2) is a transmembrane glycoprotein responsible for the vesicular monoamine uptake in the brain. This function declines in the dopaminergic mesostriatal system during normal aging, but the mechanisms responsible for this deficit are unknown. We investigated possible age-related changes in the expression and subcellular distribution of VMAT2 in the rat mesostriatal system. VMAT2 is constitutively expressed as glycosylated (75 kDa), partially glycosylated (55 kDa) and native (45 kDa) forms, they are all present in both synaptosomal compartments (synaptosomal membrane and synaptic vesicle-enriched fractions) of the striatal terminals in young rats. In aged rats, no changes were found in midbrain VMAT2mRNA and VMAT2 total protein levels in whole striatal extracts. However, its subcellular distribution and glycosylation pattern were severely modified. The three VMAT2 forms virtually disappeared from the synaptic vesicle-enriched fraction, while the 55 kDa form was accumulated in the soluble compartment. These changes may be responsible for the loss of VMAT2 activity during aging and may contribute to the high susceptibility of aged midbrain dopaminergic cells to degeneration.
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of La Laguna, 38207 La Laguna, Tenerife, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Cruz-Muros
authors.forename: Domingo
authors.initials: D
authors.lastname: Afonso-Oramas
authors.forename: Pedro
authors.initials: P
authors.lastname: Abreu
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodríguez
authors.forename: M Carmen
authors.initials: MC
authors.lastname: González
authors.forename: Tomás
authors.initials: T
authors.lastname: González-Hernández
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D006031:Glycosylation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013347:Subcellular Fractions / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D014018:Tissue Distribution; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
chemical_list: C493454:Slc18a2 protein, rat; D050493:Vesicular Monoamine Transport Proteins