Adenovirus RID-alpha activates an autonomous cholesterol regulatory mechanism that rescues defects linked to Niemann-Pick disease type C.

The Journal of Cell Biology
Nicholas L Cianciola, Cathleen R Carlin

Abstract

Host-pathogen interactions are important model systems for understanding fundamental cell biological processes. In this study, we describe a cholesterol-trafficking pathway induced by the adenovirus membrane protein RID-alpha that also subverts the cellular autophagy pathway during early stages of an acute infection. A palmitoylation-defective RID-alpha mutant deregulates cholesterol homeostasis and elicits lysosomal storage abnormalities similar to mutations associated with Niemann-Pick type C (NPC) disease. Wild-type RID-alpha rescues lipid-sorting defects in cells from patients with this disease by a mechanism involving a class III phosphatidylinositol-3-kinase. In contrast to NPC disease gene products that are localized to late endosomes/lysosomes, RID-alpha induces the accumulation of autophagy-like vesicles with a unique molecular composition. Ectopic RID-alpha regulates intracellular cholesterol trafficking at two distinct levels: the egress from endosomes and transport to the endoplasmic reticulum necessary for homeostatic gene regulation. However, RID-alpha also induces a novel cellular phenotype, suggesting that it activates an autonomous cholesterol regulatory mechanism distinct from NPC disease gene products.

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Citations

Sep 13, 2013·Molecular Biology of the Cell·Nicholas L CianciolaCathleen R Carlin
Feb 12, 2014·Human Gene Therapy·Rodinde HendrickxUrs F Greber
May 26, 2015·Biochimica Et Biophysica Acta·Daniel Wüstner, Katarzyna Solanko
Jan 1, 2015·Lipid Insights·Thomas A Lagace
Oct 15, 2019·Journal of Neurochemistry·Simon Wheeler, Dan J Sillence
Aug 23, 2020·International Journal of Molecular Sciences·Cathleen Carlin, Danny Manor
Jul 13, 2021·Frontiers in Microbiology·Kiran AvulaGulam H Syed

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Methods Mentioned

BETA
GTPase
ubiquitination
immunoprecipitation
confocal microscopy
PCR
transfection
Assay

Software Mentioned

Photoshop CS3
Adobe
Illustrator CS3
SoftMax Pro
SigmaStat
7500 System SDS
DNASTAR
MetaMorph

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