title: Distribution and ultrastructural localization of torsinA immunoreactivity in the human brain.
abstract: We have examined the distribution and ultrastructural localization of torsinA, the protein product of the TOR1A gene, in the normal adult human and Macaque brain. TorsinA immunoreactivity was visualized using a monoclonal antibody raised against a fusion protein encoding exon 4 of human torsinA. Western blot analysis of brain homogenates revealed a major species of about 39 kDa, consistent with the predicted size of glycosylated torsinA protein. By light microscopy, torsinA like-immunoreactivity was enriched in gray matter in all brain regions examined. Immunoreactivity was concentrated in the neuropil and immunopositive cell bodies were not observed. Structures particularly enriched in torsinA like-immunoreactivity included the cerebral cortex, the caudate-putamen, globus pallidus, the hippocampal formation, the thalamus, the substantia nigra and molecular cell layer of the cerebellar cortex. Cell bodies of pigmented dopamine neurons in the substantia nigra pars compacta were immunonegative. Biochemical fractionation of the human striata revealed a concentration of torsinA immunoreactivity in particulate fractions. Ultrastructural studies of the human and Macaque striata further revealed an association of torsinA immunostaining with small vesicles within axons and presynaptic terminals forming symmetric synapses. These ultrastructural studies are consistent with a pre-synaptic localization of torsinA protein in the adult striatum and are consistent with a role of torsinA in modulating striatal signaling, although the widespread localization of the protein suggests it probably also participates in signaling in other regions.
authors.affiliation: Neurology Service, Massachusetts General Hospital and Harvard Medical School, CNY 114-2300, 114 16th Street, Charlestown, MA 02129, USA. augood@helix.mgh.harvard.edu
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Augood
authors.forename: Christine E
authors.initials: CE
authors.lastname: Keller-McGandy
authors.forename: Ana
authors.initials: A
authors.lastname: Siriani
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hewett
authors.forename: Vijaya
authors.initials: V
authors.lastname: Ramesh
authors.forename: Ellen
authors.initials: E
authors.lastname: Sapp
authors.forename: Marion
authors.initials: M
authors.lastname: DiFiglia
authors.forename: Xandra O
authors.initials: XO
authors.lastname: Breakefield
authors.forename: David G
authors.initials: DG
authors.lastname: Standaert
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002352:Carrier Proteins / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D008252:Macaca fascicularis; D008854:Microscopy, Electron; D018832:Molecular Chaperones; D017072:Neostriatum / Q000378:metabolism / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins / Q000276:immunology; D009435:Synaptic Transmission / Q000502:physiology; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D002352:Carrier Proteins; D018832:Molecular Chaperones; D011993:Recombinant Fusion Proteins; C108175:TOR1A protein, human