ArticleThe Journal of biological chemistry2015
Characterization of P4 ATPase Phospholipid Translocases (Flippases) in Human and Rat Pancreatic Beta Cells: THEIR GENE SILENCING INHIBITS INSULIN SECRETION.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- A unique gating mechanism revealed by the cryo-EM structure of monomeric ATP9A flippase.The Journal of biological chemistry · 2025Article
- ATP8B1 Deficiency Causes Phosphodiesterase 4-Mediated Glucagon Resistance and Impaired Gluconeogenesis in Mouse and Human Liver.Liver international : official journal of the International Association for the Study of the Liver · 2025Article
- Article
- Weighted Burden Analysis of Rare Genetic Variants Identifies Novel Genes with Effects on BMI.Human heredity · 2025Article
- Developmental programming: Testosterone excess masculinizes female pancreatic transcriptome and function in sheep.Molecular and cellular endocrinology · 2024Article
- Physiological and Pathological Functions of TMEM30A: An Essential Subunit of P4-ATPase Phospholipid Flippases.Journal of lipids · 2023Review
- Genetic risk factors for ME/CFS identified using combinatorial analysis.Journal of translational medicine · 2022Article
- Toxoplasma gondii phosphatidylserine flippase complex ATP2B-CDC50.4 critically participates in microneme exocytosis.PLoS pathogens · 2022Article
- Review
- The phosphatidylserine flippase β-subunit Tmem30a is essential for normal insulin maturation and secretion.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Lipid flippases as key players in plant adaptation to their environment.Nature plants · 2021Review
- AP-3-dependent targeting of flippase ATP8A1 to lamellar bodies suppresses activation of YAP in alveolar epithelial type 2 cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- SNX3-retromer requires an evolutionary conserved MON2:DOPEY2:ATP9A complex to mediate Wntless sorting and Wnt secretion.Nature communications · 2018Article
- Proteomic Analysis and Functional Characterization of P4-ATPase Phospholipid Flippases from Murine Tissues.Scientific reports · 2018Article
- Control of insulin granule formation and function by the ABC transporters ABCG1 and ABCA1 and by oxysterol binding protein OSBP.Molecular biology of the cell · 2018Article
- Characterization of Acyl-CoA synthetase isoforms in pancreatic beta cells: Gene silencing shows participation of ACSL3 and ACSL4 in insulin secretion.Archives of biochemistry and biophysics · 2017Article
- P4-ATPases as Phospholipid Flippases-Structure, Function, and Enigmas.Frontiers in physiology · 2016Review
- Proteomic Analysis of the Rat Canalicular Membrane Reveals Expression of a Complex System of P4-ATPases in Liver.PloS one · 2016Article
- Flagging fusion: Phosphatidylserine signaling in cell-cell fusion.The Journal of biological chemistryReview
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The negative charge of phosphatidylserine in lipid bilayers of secretory vesicles and plasma membranes couples the domains of positively charged amino acids of secretory vesicle SNARE proteins with similar domains of plasma membrane SNARE proteins enhancing fusion of the two membranes to promote exocytosis of the vesicle contents of secretory cells. Our recent study of insulin secretory granules (ISG) (MacDonald, M. J., Ade, L., Ntambi, J. M., Ansari, I. H., and Stoker, S. W. (2015) Characterization of phospholipids in insulin secretory granules in pancreatic beta cells and their changes with glucose stimulation. J. Biol. Chem. 290, 11075-11092) suggested that phosphatidylserine and other phospholipids, such as phosphatidylethanolamine, in ISG could play important roles in docking and fusion of ISG to the plasma membrane in the pancreatic beta cell during insulin exocytosis. P4 ATPase flippases translocate primarily phosphatidylserine and, to a lesser extent, phosphatidylethanolamine across the lipid bilayers of intracellular vesicles and plasma membranes to the cytosolic leaflets of these membranes. CDC50A is a protein that forms a heterodimer with P4 ATPases to enhance their translocase catalytic activity. We found that the predominant P4 ATPases in pure pancreatic beta cells and human and rat pancreatic islets were ATP8B1, ATP8B2, and ATP9A. ATP8B1 and CDC50A were highly concentrated in ISG. ATP9A was concentrated in plasma membrane. Gene silencing of individual P4 ATPases and CDC50A inhibited glucose-stimulated insulin release in pure beta cells and in human pancreatic islets. This is the first characterization of P4 ATPases in beta cells. The results support roles for P4 ATPases in translocating phosphatidylserine to the cytosolic leaflets of ISG and the plasma membrane to facilitate the docking and fusion of ISG to the plasma membrane during insulin exocytosis.
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