title: PARK10 candidate RNF11 is expressed by vulnerable neurons and localizes to Lewy bodies in Parkinson disease brain.
abstract: The PARK10 locus is associated with idiopathic Parkinson disease (PD), but the responsible gene remains to be identified. Genes associated with familial PD, as well as biochemical evidence from sporadic PD and animal models, have implicated components of the ubiquitin-proteasome system in PD pathogenesis. One attractive candidate gene at the PARK10 locus is RING-Finger Protein 11 (RNF11), the deduced amino acid sequence of which predicts a RING-H2 domain common to E3 ubiquitin ligases such as parkin. To facilitate understanding of this protein and its possible role in PD, we characterized the expression and localization of RNF11 in brain. We detected RNF11 transcript and protein and provided the first direct evidence that RNF11 is expressed in brain. Immunohistochemical analysis of RNF11 protein in rat and human brain, using 2 different antibodies, corroborated the mRNA findings. Both antibodies show that RNF11 is restricted to neurons and excluded from white matter. Moreover, RNF11 is expressed by vulnerable neurons of the substantia nigra and sequestered into Lewy bodies in brains of patients with idiopathic PD. Collectively, these findings identify RNF11 as a strong candidate gene at the PARK10 locus and highlight its potential significance in the development of the common form of PD.
authors.affiliation: Center for Neurodegenerative Disease, Graduate Program in Neuroscience, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Leah R
authors.initials: LR
authors.lastname: Anderson
authors.forename: Ranjita
authors.initials: R
authors.lastname: Betarbet
authors.forename: Marla
authors.initials: M
authors.lastname: Gearing
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Gulcher
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Hicks
authors.forename: Kári
authors.initials: K
authors.lastname: Stefánsson
authors.forename: James J
authors.initials: JJ
authors.lastname: Lah
authors.forename: Allan I
authors.initials: AI
authors.lastname: Levey
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D001344:Autopsy; D015152:Blotting, Northern; D001923:Brain Chemistry / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D016631:Lewy Bodies / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D016612:Paraffin Embedding; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D051381:Rats
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C404508:RNF11 protein, human