RRC ID 22042
著者 Hopkins PC.
タイトル Neurodegeneration in a Drosophila model for the function of TMCC2, an amyloid protein precursor-interacting and apolipoprotein E-binding protein.
ジャーナル PLoS One
Abstract We previously identified TMCC2 as a protein that interacted differentially with normal versus Alzheimer's disease-risk forms of both apolipoprotein E (apoE) and the amyloid protein precursor (APP). We hypothesized that disrupted function of TMCC2 would affect neurodegeneration. To test this hypothesis, we investigated the Drosophila orthologue of TMCC2, that we have named Dementin. We showed that Dementin interacts genetically both with human APP and its Drosophila orthologue, the APP-like protein (APPL). Ectopic expression of Dementin in Drosophila rescued developmental and behavioral defects caused by expression of human APP. Both a hypomorphic lethal mutation in the dementin gene (dmtn(1)) and RNAi for Dementin caused the accumulation of fragments derived from APPL. We found that Dementin was required for normal development of the brain, and that glial Dementin was required for development of the Drosophila medulla neuropil. Expression of wild-type Dementin in either the neurons or glia of dmtn(1) flies rescued developmental lethality. Adult dmtn(1) flies rescued by expression of wild-type Dementin in glia, i.e. whose neurons expressed only dmtn(1), showed pathological features resembling early onset Alzheimer's disease, accumulation of abnormal APPL metabolites, synaptic pathology, mis-localized microtubule-binding proteins, neurodegeneration, and early death.
巻・号 8(2)
ページ e55810
公開日 2013-2-7
DOI 10.1371/journal.pone.0055810
PII PONE-D-12-04755
解説 PMC3567013
PMID 23409049
PMC PMC3567013
MeSH Alleles Alzheimer Disease / genetics Alzheimer Disease / metabolism Amyloid beta-Protein Precursor / genetics Amyloid beta-Protein Precursor / metabolism* Animals Apolipoproteins E / genetics Apolipoproteins E / metabolism* Brain / embryology Brain / metabolism Carrier Proteins / classification Carrier Proteins / genetics Carrier Proteins / metabolism* Central Nervous System / metabolism Disease Models, Animal Drosophila Drosophila Proteins / classification Drosophila Proteins / genetics Drosophila Proteins / metabolism* Epistasis, Genetic Gene Expression Profiling Gene Order Male Multigene Family Phylogeny Protein Binding RNA Interference
IF 2.74
引用数 11
WOS 分野 NEUROSCIENCES
リソース情報
ショウジョウバエ NP6590 (DGRC#105275)