RRC ID 46531
著者 Wiese M, Antebi A, Zheng H.
タイトル Regulation of neuronal APL-1 expression by cholesterol starvation.
ジャーナル PLoS One
Abstract BACKGROUND:Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of β-amyloid plaques composed primarily of the amyloid-β peptide, a cleavage product of amyloid precursor protein (APP). While mutations in APP lead to the development of Familial Alzheimer's Disease (FAD), sporadic AD has only one clear genetic modifier: the ε4 allele of the apolipoprotein E (ApoE) gene. Cholesterol starvation in Caenorhabditis elegans leads to molting and arrest phenotypes similar to loss-of-function mutants of the APP ortholog, apl-1 (amyloid precursor-like protein 1), and lrp-1 (lipoprotein receptor-related protein 1), suggesting a potential interaction between apl-1 and cholesterol metabolism.
METHODOLOGY/PRINCIPAL FINDINGS:Previously, we found that RNAi knock-down of apl-1 leads to aldicarb hypersensitivity, indicating a defect in synaptic function. Here we find the same defect is recapitulated during lrp-1 knock-down and by cholesterol starvation. A cholesterol-free diet or loss of lrp-1 directly affects APL-1 levels as both lead to loss of APL-1::GFP fluorescence in neurons. However, loss of cholesterol does not affect global transcription or protein levels as seen by qPCR and Western blot.
CONCLUSIONS:Our results show that cholesterol and lrp-1 are involved in the regulation of synaptic transmission, similar to apl-1. Both are able to modulate APL-1 protein levels in neurons, however cholesterol changes do not affect global apl-1 transcription or APL-1 protein indicating the changes are specific to neurons. Thus, regulation of synaptic transmission and molting by LRP-1 and cholesterol may be mediated by their ability to control APL-1 neuronal protein expression.
巻・号 7(2)
ページ e32038
公開日 2012-1-1
DOI 10.1371/journal.pone.0032038
PII PONE-D-11-23171
PMID 22363792
PMC PMC3283687
MeSH Aldicarb / pharmacology Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / drug effects Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cholesterol / deficiency* Cholesterol / pharmacology Diet Gene Expression Regulation / drug effects Gene Knockdown Techniques Green Fluorescent Proteins / metabolism Membrane Proteins / genetics Membrane Proteins / metabolism* Molting / drug effects Neurons / cytology Neurons / drug effects Neurons / metabolism* RNA Interference / drug effects Synaptic Transmission / drug effects Transcription, Genetic / drug effects
IF 2.74
引用数 7
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
線虫 tm385