PARK10 candidate RNF11 is expressed by vulnerable neurons and localizes to Lewy bodies in Parkinson disease brain.
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.
Anderson
Leah R
LR
Center for Neurodegenerative Disease, Graduate Program in Neuroscience, Emory University, Atlanta, Georgia 30322, USA.
Betarbet
Ranjita
R
Gearing
Marla
M
Gulcher
Jeffrey
J
Hicks
Andrew A
AA
Stefánsson
Kári
K
Lah
James J
JJ
Levey
Allan I
AI
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
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C404508:RNF11 protein, human