BTN1, the Saccharomyces cerevisiae homolog to the human Batten disease gene, is involved in phospholipid distribution

Autor: Sergio Padilla-Lopez, David A. Pearce, Deanna Langager, Chun-Hung Chan
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Vacuolar Proton-Translocating ATPases
Saccharomyces cerevisiae Proteins
Endosome
Membrane lipids
Genes
Fungal
Neuroscience (miscellaneous)
lcsh:Medicine
Medicine (miscellaneous)
Biological Transport
Active
Vacuole
Saccharomyces cerevisiae
Mitochondrion
Biology
Endoplasmic Reticulum
Models
Biological
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
chemistry.chemical_compound
Membrane Lipids
0302 clinical medicine
Immunology and Microbiology (miscellaneous)
Neuronal Ceroid-Lipofuscinoses
Cyclins
lcsh:Pathology
Humans
DNA
Fungal
Phospholipids
030304 developmental biology
Phosphatidylethanolamine
0303 health sciences
Membrane Glycoproteins
Base Sequence
Endoplasmic reticulum
lcsh:R
Phosphatidylserine
Cell biology
Mitochondria
chemistry
Biochemistry
Membrane protein
Vacuoles
030217 neurology & neurosurgery
Metabolic Networks and Pathways
lcsh:RB1-214
Research Article
Molecular Chaperones
Zdroj: Disease Models & Mechanisms
Disease Models & Mechanisms, Vol 5, Iss 2, Pp 191-199 (2012)
ISSN: 1754-8411
1754-8403
Popis: SUMMARY BTN1, the yeast homolog to human CLN3 (which is defective in Batten disease), has been implicated in the regulation of vacuolar pH, potentially by modulating vacuolar-type H+-ATPase (V-ATPase) activity. However, we report that Btn1p and the V-ATPase complex do not physically interact, suggesting that any influence that Btn1p has on V-ATPase is indirect. Because membrane lipid environment plays a crucial role in the activity and function of membrane proteins, we investigated whether cells lacking BTN1 have altered membrane phospholipid content. Deletion of BTN1 (btn1-Δ) led to a decreased level of phosphatidylethanolamine (PtdEtn) in both mitochondrial and vacuolar membranes. In yeast there are two phosphatidylserine (PtdSer) decarboxylases, Psd1p and Psd2p, and these proteins are responsible for the synthesis of PtdEtn in mitochondria and Golgi-endosome, respectively. Deletion of both BTN1 and PSD1 (btn1-Δ psd1-Δ) led to a further decrease in levels of PtdEtn in ER membranes associated to mitochondria (MAMs), with a parallel increase in PtdSer. Fluorescent-labeled PtdSer (NBD-PtdSer) transport assays demonstrated that transport of NBD-PtdSer from the ER to both mitochondria and endosomes and/or vacuole is affected in btn1-Δ cells. Moreover, btn1-Δ affects the synthesis of PtdEtn by the Kennedy pathway and impairs the ability of psd1-Δ cells to restore PtdEtn to normal levels in mitochondria and vacuoles by ethanolamine addition. In summary, lack of Btn1p alters phospholipid levels and might play a role in regulating their subcellular distribution.
Databáze: OpenAIRE
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