RRC ID 32417
Author Ma Z, Liu Z, Huang X.
Title Membrane phospholipid asymmetry counters the adverse effects of sterol overloading in the Golgi membrane of Drosophila.
Journal Genetics
Abstract Cholesterol and phospholipids serve as structural and functional components of cellular membranes in all eukaryotes. Heterogeneity in cholesterol and phospholipid content both within and between different organelles is an important characteristic of eukaryotic membranes. How this heterogeneity is achieved and orchestrated to maintain proper cellular physiology remains poorly understood. We previously found that overexpression of the Drosophila oxysterol-binding protein (OSBP) leads to sterol accumulation in the Golgi apparatus. Here, we show that Osbp overexpression in a set of neuroendocrine neurons compromises the function of the Golgi apparatus. It impairs trafficking of the neuropeptide bursicon and results in post-eclosion behavior defects characterized by unexpanded wings. We performed a genetic screen to identify modifiers that suppress the unexpanded wing phenotype. A putative phospholipid flippase-encoding gene, CG33298, was validated, suggesting that a membrane-asymmetry-directed mechanism balances cholesterol chaos within the Golgi membranes. Since the functional connection between cholesterol metabolism and the activity of phospholipid flippase has been implicated in studies in yeast and worms, our findings here support an evolutionarily conserved causal link between cholesterol homeostasis and phospholipid asymmetry that maintains normal cellular physiology.
Volume 190(4)
Pages 1299-308
Published 2012-4
DOI 10.1534/genetics.111.137687
PII genetics.111.137687
PMID 22234859
PMC PMC3316644
MeSH Animals Animals, Genetically Modified / genetics Animals, Genetically Modified / metabolism Animals, Genetically Modified / physiology Carrier Proteins / metabolism* Cholesterol / metabolism* Drosophila / genetics Drosophila / metabolism* Drosophila / physiology Drosophila Proteins / metabolism* Gene Expression Regulation Genes, Insect Golgi Apparatus / metabolism* Golgi Apparatus / physiology Homeostasis Intracellular Membranes / metabolism Invertebrate Hormones / metabolism Male Neurons / cytology Neurons / metabolism Neuropeptides / genetics Neuropeptides / metabolism Phospholipids / metabolism* Protein Transport Secretory Vesicles / genetics Secretory Vesicles / metabolism Wings, Animal / physiology
IF 4.075
Times Cited 8
Drosophila DGRC#205841