Dynamic formation of ER–PM junctions presents a lipid phosphatase to regulate phosphoinositides

Dickson, Eamonn J.; Jensen, Jill B.; Vivas, Oscar; Kruse, Martin; Traynor‐Kaplan, Alexis; Hille, Bertil

doi:10.1083/jcb.201508106

Cited by 84 publications

(105 citation statements)

References 68 publications

(134 reference statements)

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“…Surprisingly, transformed cell lines in culture, even though they are mammalian, have diminished 38:4 in their phosphoinositides. We showed this here for nearly confluent CHO and tsA201 cells (both having 36:1 and 36:2) [38], and a similar “arachidonic acid deficiency” has been reported before for RAW264.7 cells, MCF10a breast cancer cells, and HeLa cells [7, 16, 18]. Then we found in rapidly growing, 40% confluent tsA201 cells, that 38:4 is in fact dominant in the phosphoinositides, as it is in mammalian primary cells, and that the shift to shorter chain and less unsaturated fatty acids develops subsequently.…”

Section: Discussionmentioning

confidence: 67%

“…Altogether, with these methods, we achieved a detection limit below 20 pg (~20 fmole) injected into the MS machine. We have used these methods in several recent papers [38–40]. …”

Section: Discussionmentioning

confidence: 99%

“…Both in RAW264.7 cells and in flies, adding polyunsaturated fatty acids to the diet will increase the prevalence of unsaturated acyl chains in glycerophospholipids [14, 18]. The relative amounts of different phosphoinositide classes are changed in cells expressing mutant or transfected lipid phosphatases [5, 38]. Finally rapid changes of phosphoinositide signaling, inositol phosphate abundance, and membrane viscosity occur during the cell cycle perhaps through an increase of cells in G0/G1, and conversely, the cell cycle may be altered by phosphoinositides [44–49].…”

Section: Discussionmentioning

confidence: 99%

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Fatty-acyl chain profiles of cellular phosphoinositides

Traynor‐Kaplan

Kruse

Dickson

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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120

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Phosphoinositides are rapidly turning-over phospholipids that play key roles in intracellular signaling and modulation of membrane effectors. Through technical refinements we have improved sensitivity in the analysis of the phosphoinositide PI, PIP, and PIP2 pools from living cells using mass spectrometry. This has permitted further resolution in phosphoinositide lipidomics from cell cultures and small samples of tissue. The technique includes butanol extraction, derivatization of the lipids, post-column infusion of sodium to stabilize formation of sodiated adducts, and electrospray ionization mass spectrometry in multiple reaction monitoring mode, achieving a detection limit of 20 pg. We describe the spectrum of fatty-acyl chains in the cellular phosphoinositides. Consistent with previous work in other mammalian primary cells, the 38:4 fatty-acyl chains dominate in the phosphoinositides of the pineal gland and of superior cervical ganglia, and many additional fatty acid combinations are found at low abundance. However, Chinese hamster ovary cells and human embryonic kidney cells (tsA201) in culture have different fatty-acyl chain profiles that change with growth state. Their 38:4 lipids lose their dominance as cultures approach confluence. The method has good time resolution and follows well the depletion in < 20 s of both PIP2 and PIP that results from strong activation of Gq-coupled receptors. The receptor-activated phospholipase C exhibits no substrate selectivity among the various fatty-acyl chain combinations.

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Section: Discussionmentioning

confidence: 67%

“…Altogether, with these methods, we achieved a detection limit below 20 pg (~20 fmole) injected into the MS machine. We have used these methods in several recent papers [38–40]. …”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Fatty-acyl chain profiles of cellular phosphoinositides

Traynor‐Kaplan

Kruse

Dickson

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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120

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“…This may occur via delivery of PI4P to the ER by the transport activity of these proteins (Chung et al, 2015; Mesmin et al, 2013; Moser von Filseck et al, 2015) or, as proposed by others, by in trans action of Sac1 on the adjacent membrane (Dickson et al, 2016; Stefan et al, 2011). In yeast, deletion of the two VAP homologs (Scs2 and Scs22) results in strong PI4P elevations, with the bulk of excessive PI4P being localized at the plasma membrane (Stefan et al, 2011).…”

Section: Discussionmentioning

confidence: 93%

Endosome-ER Contacts Control Actin Nucleation and Retromer Function through VAP-Dependent Regulation of PI4P

Dong

Saheki

Swarup

et al. 2016

Cell

336

368

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SUMMARY VAP (VAPA and VAPB) is an evolutionarily conserved endoplasmic reticulum (ER)-anchored protein that helps generate tethers between the ER and other membranes through which lipids are exchanged across adjacent bilayers. Here, we report that by regulating PI4P levels on endosomes, VAP affects WASH-dependent actin nucleation on these organ-elles and the function of the retromer, a protein coat responsible for endosome-to-Golgi traffic. VAP is recruited to retromer budding sites on endosomes via an interaction with the retromer SNX2 subunit. Cells lacking VAP accumulate high levels of PI4P, actin comets, and trans-Golgi proteins on endosomes. Such defects are mimicked by downregulation of OSBP, a VAP interactor and PI4P transporter that participates in VAP-dependent ER-endosomes tethers. These results reveal a role of PI4P in retromer-/WASH-dependent budding from endosomes. Collectively, our data show how the ER can control budding dynamics and association with the cyto-skeleton of another membrane by direct contacts leading to bilayer lipid modifications.

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“…Finally, our modeling omits several significant cell-biological complexities that would compromise a desire for more perfect fits. Our previous work, as well as the work of others, shows that the four phosphoinositide species we have discussed actually have several dynamic pools on different membranes and organelles that exchange with each other by trafficking or lipid exchange in tens of seconds (38,39). Further, we and others have shown that when phosphoinositide pools are depleted by activating phospholipase C, the cellular lipid kinases are accelerated considerably (29,40).…”

Section: Discussionmentioning

confidence: 99%

Phosphoinositide 5- and 3-phosphatase activities of a voltage-sensing phosphatase in living cells show identical voltage dependence

Keum

Kruse

Kim

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Voltage-sensing phosphatases (VSPs) are homologs of phosphatase and tensin homolog (PTEN), a phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] 3-phosphatase. However, VSPs have a wider range of substrates, cleaving 3-phosphate from PI(3,4)P2 and probably PI(3,4,5)P3 as well as 5-phosphate from phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and PI(3,4,5)P3 in response to membrane depolarization. Recent proposals say these reactions have differing voltage dependence. Using Förster resonance energy transfer probes specific for different PIs in living cells with zebrafish VSP, we quantitate both voltage-dependent 5- and 3-phosphatase subreactions against endogenous substrates. These activities become apparent with different voltage thresholds, voltage sensitivities, and catalytic rates. As an analytical tool, we refine a kinetic model that includes the endogenous pools of phosphoinositides, endogenous phosphatase and kinase reactions connecting them, and four exogenous voltage-dependent 5- and 3-phosphatase subreactions of VSP. We show that apparent voltage threshold differences for seeing effects of the 5- and 3-phosphatase activities in cells are not due to different intrinsic voltage dependence of these reactions. Rather, the reactions have a common voltage dependence, and apparent differences arise only because each VSP subreaction has a different absolute catalytic rate that begins to surpass the respective endogenous enzyme activities at different voltages. For zebrafish VSP, our modeling revealed that 3-phosphatase activity against PI(3,4,5)P3 is 55-fold slower than 5-phosphatase activity against PI(4,5)P2; thus, PI(4,5)P2 generated more slowly from dephosphorylating PI(3,4,5)P3 might never accumulate. When 5-phosphatase activity was counteracted by coexpression of a phosphatidylinositol 4-phosphate 5-kinase, there was accumulation of PI(4,5)P2 in parallel to PI(3,4,5)P3 dephosphorylation, emphasizing that VSPs can cleave the 3-phosphate of PI(3,4,5)P3.

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Dynamic formation of ER–PM junctions presents a lipid phosphatase to regulate phosphoinositides

Cited by 84 publications

References 68 publications

Fatty-acyl chain profiles of cellular phosphoinositides

Fatty-acyl chain profiles of cellular phosphoinositides

Endosome-ER Contacts Control Actin Nucleation and Retromer Function through VAP-Dependent Regulation of PI4P

Phosphoinositide 5- and 3-phosphatase activities of a voltage-sensing phosphatase in living cells show identical voltage dependence

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