Ceramide kinase regulates phospholipase C and phosphatidylinositol 4, 5, bisphosphate in phototransduction

Dasgupta, Ujjaini; Bamba, Takeshi; Chiantia, Salvatore; Karim, Pusha; Tayoun, Ahmad N. Abou; Yonamine, Ikuko; Rawat, Satinder S.; Rao, Raghavendra Pralhada; Nagashima, Kunio; Fukusaki, Eiichiro; Puri, Vishwajeet; Dolph, Patrick J.; Schwille, Petra; Acharya, Jairaj; Acharya, Usha

doi:10.1073/pnas.0911028106

Cited by 45 publications

(50 citation statements)

References 35 publications

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“…The primary evidence of PIP2 enrichment in lipid microdomains is based on the observation that PIP2 is enriched in detergent insoluble fractions of the plasma membrane (Hope and Pike, 1996; Klopfenstein et al, 2002; Pike and Casey, 1996) and is delocalized when cholesterol is depleted from the cell membrane (Liu et al, 1998; Pike and Miller, 1998). This hypothesis is supported by a later observation that PIP2 form clusters in the presence of cholesterol alone (Dasgupta et al, 2009). Paradoxically, fluorescent PIP 2 is found to be excluded from the liquidordered phase of a model membrane in the presence of cholesterol (Levental et al, 2009).…”

Section: Introductionsupporting

confidence: 58%

Counterion-mediated cluster formation by polyphosphoinositides

Wang

Slochower

Janmey

2014

Chemistry and Physics of Lipids

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Polyphosphoinositides (PPI) and in particular PI(4,5)P2, are among the most highly charged molecules in cell membranes, are important in many cellular signaling pathways, and are frequently targeted by peripheral polybasic proteins for anchoring through electrostatic interactions. Such interactions between PIP2 and proteins containing polybasic stretches depend on the physical state and the lateral distribution of PIP2 within the inner leaflet of the cell's lipid bilayer. The physical chemical properties of PIP2 such as pH-dependent changes in headgroup ionization and area per molecule as determined by experiments together with molecular simulations that predict headgroup conformations at various ionization states have revealed the electrostatic properties and phase behavior of PIP2-containing membranes. This review focuses on recent experimental and computational developments in defining the physical chemistry of PIP2 and its interactions with counterions. Ca2+-induced changes in PIP2 charge, conformation, and lateral structure within the membrane are documented by numerous experimental and computational studies. A simplified electrostatic model successfully predicts the Ca2+-driven formation of PIP2 clusters but cannot account for the different effects of Ca2+ and Mg2+ on PIP2-containing membranes. A more recent computational study is able to see the difference between Ca2+ and Mg2+ binding to PIP2 in the absence of a membrane and without cluster formation. Spectroscopic studies suggest that divalent cation- and multivalent polyamine-induced changes in the PIP2 lateral distribution in model membrane are also different, and not simply related to the net charge of the counterion. Among these differences is the capacity of Ca2+ but not other polycations to induce nm scale clusters of PIP2 in fluid membranes. Recent super resolution optical studies show that PIP2 forms nanoclusters in the inner leaflet of a plasma membrane with a similar size distribution as those induced by Ca2+ in model membranes. The mechanisms by which PIP2 forms nanoclusters and other structures inside a cell remain to be determined, but the unique electrostatic properties of PIP2 and its interactions with multivalent counterions might have particular physiological relevance.

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Section: Introductionsupporting

confidence: 58%

Counterion-mediated cluster formation by polyphosphoinositides

Wang

Slochower

Janmey

2014

Chemistry and Physics of Lipids

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“…Reproductive defects have also been observed in response to SPL knockdown in Caenorhabditis elegans 33. A mutation in the Drosophila CERK gene was recently shown to be associated with photoreceptor degeneration 62. In the context of developmental programs lacking obvious S1P receptors, these phenotypes most likely represent receptor-independent effects that may result when ceramide and/or other sphingolipid intermediates perturb membrane structure, calcium homeostasis and/or protein functions.…”

Section: S1p In Invertebrate Developmentmentioning

confidence: 99%

An update on sphingosine-1-phosphate and other sphingolipid mediators

2010

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Sphingolipids comprise a complex family of naturally occurring molecules that are enriched in lipid rafts and contribute to their unique biochemical properties. Membrane sphingolipids also serve as a reservoir for bioactive metabolites including sphingosine, ceramide, sphingosine-1-phosphate and ceramide-1-phosphate. Among these, sphingosine-1-phosphate has emerged as a central regulator of mammalian biology. Sphingosine-1-phosphate is essential for mammalian brain and cardiac development and maturation of the systemic circulatory system and lymphatics. In addition, sphingosine-1-phosphate contributes to trafficking and effector functions of lymphocytes and other hematopoietic cells and protects against various forms of tissue injury. However, sphingosine-1-phosphate is also an oncogenic lipid that promotes tumor growth and progression. Recent preclinical and clinical investigations using pharmacological agents that target sphingosine-1-phosphate, its receptors, and the enzymes required for its biosynthesis and degradation demonstrate the promise and potential risks of modulating sphingosine-1-phosphate signaling in treatment strategies for autoimmunity, cancer, cardiovascular disease and other pathological conditions.

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“…Approximately 1 g of protein sample was injected, and experiments were run in triplicate. For the two-dimensional separations, 10 l of NH 4 Cl salt bumps were applied (10,20,30,40,60,80,120, and 400 mM), and around 1 g of sample was loaded onto a 0.32 ϫ 100-mm SCX column (5-m particle size; Column Technology Inc.). A precolumn (DIONEX, Pep Map100 C18, 0.30 ϫ 5 mm, 5-m particle size) was brought inline with the analytical column, and a 3-h gradient (solvent A, 0.1% formic acid in water; solvent B, 0.1% formic acid in acetonitrile) from 5 to 30% solvent B was used for separating the peptides.…”

Section: Methodsmentioning

confidence: 99%

Mass Spectrometric Studies on Epigenetic Interaction Networks in Cell Differentiation

Xiong

Darwanto

Sharma

et al. 2011

Journal of Biological Chemistry

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Arrest of cell differentiation is one of the leading causes of leukemia and other cancers. Induction of cell differentiation using pharmaceutical agents has been clinically attempted for the treatment of these cancers. Epigenetic regulation may be one of the underlying molecular mechanisms controlling cell proliferation or differentiation. Here, we report on the use of proteomics-based differential protein expression analysis in conjunction with quantification of histone modifications to decipher the interconnections among epigenetic modifications, their modifying enzymes or mediators, and changes in the associated pathways/networks that occur during cell differentiation. During phorbol-12-myristate 13-acetate-induced differentiation of U937 cells, fatty acid synthesis and its metabolic processing, the clathrin-coated pit endocytosis pathway, and the ubiquitin/26 S proteasome degradation pathways were up-regulated. In addition, global histone H3/H4 acetylation and H2B ubiquitination were down-regulated concomitantly with impaired chromatin remodeling machinery, RNA polymerase II complexes, and DNA replication. Differential protein expression analysis established the networks linking histone hypoacetylation to the down-regulated expression/activity of p300 and linking histone H2B ubiquitination to the RNA polymerase II-associated FACT-RTF1-PAF1 complex. Collectively, our approach has provided an unprecedentedly systemic set of insights into the role of epigenetic regulation in leukemia cell differentiation.Both histone acetylation and H2B ubiquitination are associated with gene activation as defined by the "histone code" and "cross-talk" theories (1). As demonstrated previously in Berk's laboratory (2), small interfering RNA (siRNA)-mediated dual knockdown of CBP 5 and p300 resulted in specific histone H3Lys-18 hypoacetylation in vivo in both IMR90 and HeLa cells, indicating that p300/CBP, possibly together with their closely associated protein PCAF, are the major histone acetyltransferases required for maintaining global H3 Lys-18 acetylation.On the other hand, the putative histone H2B ubiquitination enzyme, UBCH6 (also known as UBE2E1), physically interacts with RNF20/40 (homologs of Bre1, the E3 ligase in yeast) and PAF1 to form a trimeric complex, which colocalizes with RNA polymerase II at transcriptionally active genes (3). RTF1, which has a function similar to Rad6 (mediates ubiquitination at lysine 123 of H2B in yeast) and is a component of the PAF1/RNA polymerase II complex, cooperatively interacts with RNF20/40, and FACT (facilitates chromatin transcription) to regulate H2B ubiquitination (4 -8).

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Ceramide kinase regulates phospholipase C and phosphatidylinositol 4, 5, bisphosphate in phototransduction

Cited by 45 publications

References 35 publications

Counterion-mediated cluster formation by polyphosphoinositides

Counterion-mediated cluster formation by polyphosphoinositides

An update on sphingosine-1-phosphate and other sphingolipid mediators

Mass Spectrometric Studies on Epigenetic Interaction Networks in Cell Differentiation

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