ArticleThe Journal of cell biology2002
Dual role for phosphoinositides in regulation of yeast and mammalian phospholipase D enzymes.
Article in The Journal of cell biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 100 citations in OpenAlex.
- Article
- Subcellular Cartography of the Phosphoinositide Multiverse.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026Review
- Recruitment of the lipid kinase Mss4 to the meiotic spindle pole promotes prospore membrane formation inMolecular biology of the cell · 2023Article
- Arabidopsis PLDζ1 and PLDζ2 localize to post-Golgi membrane compartments in a partially overlapping manner.Plant molecular biology · 2022Article
- Structure and regulation of human phospholipase D.Advances in biological regulation · 2021Review
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- PLD2-PI(4,5)P2 interactions in fluid phase membranes: Structural modeling and molecular dynamics simulations.PloS one · 2020Article
- Antimicrobial agent triclosan suppresses mast cell signaling via phospholipase D inhibition.Journal of applied toxicology : JAT · 2019Article
- Regulation of PLPP3 gene expression by NF-κB family transcription factors.The Journal of biological chemistry · 2019Article
- Phosphatidylinositol 3,5-bisphosphate regulates the transition between trans-SNARE complex formation and vacuole membrane fusion.Molecular biology of the cell · 2019Article
- PLD2 regulates microtubule stability and spindle migration in mouse oocytes during meiotic division.PeerJ · 2017Article
- Physiological and pathophysiological roles for phospholipase D.Journal of lipid research · 2015Review
- Two sites of action for PLD2 inhibitors: The enzyme catalytic center and an allosteric, phosphoinositide biding pocket.Biochimica et biophysica acta · 2015Article
- Mechanism of enzymatic reaction and protein-protein interactions of PLD from a 3D structural model.Cellular signalling · 2015Article
- Phospholipase D signaling pathways and phosphatidic acid as therapeutic targets in cancer.Pharmacological reviews · 2014Review
- Thematic minireview series on phospholipase D and cancer.The Journal of biological chemistry · 2014Article
- Role of phospholipase d in g-protein coupled receptor function.Membranes · 2014Article
- A neurotoxic glycerophosphocholine impacts PtdIns-4, 5-bisphosphate and TORC2 signaling by altering ceramide biosynthesis in yeast.PLoS genetics · 2014Article
- The hydrophobic amino acids involved in the interdomain association of phospholipase D1 regulate the shuttling of phospholipase D1 from vesicular organelles into the nucleus.Experimental & molecular medicine · 2012Article
- SPO71 mediates prospore membrane size and maturation in Saccharomyces cerevisiae.Eukaryotic cell · 2012Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Phospholipase D (PLD) generates lipid signals that coordinate membrane trafficking with cellular signaling. PLD activity in vitro and in vivo is dependent on phosphoinositides with a vicinal 4,5-phosphate pair. Yeast and mammalian PLDs contain an NH2-terminal pleckstrin homology (PH) domain that has been speculated to specify both subcellular localization and regulation of PLD activity through interaction with phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2). We report that mutation of the PH domains of yeast and mammalian PLD enzymes generates catalytically active PI(4,5)P2-regulated enzymes with impaired biological functions. Disruption of the PH domain of mammalian PLD2 results in relocalization of the protein from the PI(4,5)P2-containing plasma membrane to endosomes. As a result of this mislocalization, mutations within the PH domain render the protein unresponsive to activation in vivo. Furthermore, the integrity of the PH domain is vital for yeast PLD function in both meiosis and secretion. Binding of PLD2 to model membranes is enhanced by acidic phospholipids. Studies with PLD2-derived peptides suggest that this binding involves a previously identified polybasic motif that mediates activation of the enzyme by PI(4,5)P2. By comparison, the PLD2 PH domain binds PI(4,5)P2 with lower affinity but sufficient selectivity to function in concert with the polybasic motif to target the protein to PI(4,5)P2-rich membranes. Phosphoinositides therefore have a dual role in PLD regulation: membrane targeting mediated by the PH domain and stimulation of catalysis mediated by the polybasic motif.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.