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PI(4,5)P2

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https://www.readbyqxmd.com/read/29320679/effect-of-h-bond-donor-lipids-on-phosphatidylinositol-3-4-5-trisphosphate-ionization-and-clustering
#1
Zachary T Graber, Joseph Thomas, Emily Johnson, Arne Gericke, Edgar E Kooijman
The phosphoinositide, phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3), is a key signaling lipid in the inner leaflet of the cell plasma membrane, regulating diverse signaling pathways including cell growth and migration. In this study we investigate the impact of the hydrogen-bond donor lipids phosphatidylethanolamine (PE) and phosphatidylinositol (PI) on the charge and phase behavior of PI(3,4,5)P3. PE and PI can interact with PI(3,4,5)P3 through hydrogen-bond formation, leading to altered ionization behavior and charge distribution within the PI(3,4,5)P3 headgroup...
January 9, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29277655/phosphatidylinositol-4-5-bisphosphate-cholesterol-and-fatty-acids-modulate-the-calcium-activated-chloride-channel-tmem16a-ano1
#2
José J De Jesús-Pérez, Silvia Cruz-Rangel, Ángeles E Espino-Saldaña, Ataúlfo Martínez-Torres, Zhiqiang Qu, H Criss Hartzell, Nancy E Corral-Fernandez, Patricia Pérez-Cornejo, Jorge Arreola
The TMEM16A-mediated Ca2+-activated Cl- current drives several important physiological functions. Membrane lipids regulate ion channels and transporters but their influence on members of the TMEM16 family is poorly understood. Here we have studied the regulation of TMEM16A by phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), cholesterol, and fatty acids using patch clamp, biochemistry and fluorescence microscopy. We found that depletion of membrane PI(4,5)P2 causes a decline in TMEM16A current that is independent of cytoskeleton, but is partially prevented by removing intracellular Ca2+...
December 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29229838/architecture-of-the-human-pi4kiii%C3%AE-lipid-kinase-complex
#3
Joshua A Lees, Yixiao Zhang, Michael S Oh, Curtis M Schauder, Xiaoling Yu, Jeremy M Baskin, Kerry Dobbs, Luigi D Notarangelo, Pietro De Camilli, Thomas Walz, Karin M Reinisch
Plasma membrane (PM) phosphoinositides play essential roles in cell physiology, serving as both markers of membrane identity and signaling molecules central to the cell's interaction with its environment. The first step in PM phosphoinositide synthesis is the conversion of phosphatidylinositol (PI) to PI4P, the precursor of PI(4,5)P2 and PI(3,4,5)P3 This conversion is catalyzed by the PI4KIIIα complex, comprising a lipid kinase, PI4KIIIα, and two regulatory subunits, TTC7 and FAM126. We here report the structure of this complex at 3...
December 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29223474/fine-tuning-of-store-operated-calcium-entry-by-fast-and-slow-ca2-dependent-inactivation-involvement-of-saraf
#4
REVIEW
Isaac Jardín, Letizia Albarran, Ginés M Salido, Jose J López, Stewart O Sage, Juan A Rosado
Store-operated Ca2+ entry (SOCE) is a functionally relevant mechanism for Ca2+ influx present in electrically excitable and non-excitable cells. Regulation of Ca2+ entry through store-operated channels is essential to maintain an appropriate intracellular Ca2+ homeostasis and prevent cell damage. Calcium-release activated channels exhibit Ca2+-dependent inactivation mediated by two temporally separated mechanisms: fast Ca2+-dependent inactivation takes effect in the order of milliseconds and involves the interaction of Ca2+ with residues in the channel pore while slow Ca2+-dependent inactivation (SCDI) develops over tens of seconds, requires a global rise in [Ca2+]cyt and is a mechanism regulated by mitochondria...
December 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29222176/ca2-releases-e-syt1-autoinhibition-to-couple-er-plasma-membrane-tethering-with-lipid-transport
#5
Xin Bian, Yasunori Saheki, Pietro De Camilli
The extended synaptotagmins (E-Syts) are endoplasmic reticulum (ER) proteins that bind the plasma membrane (PM) via C2 domains and transport lipids between them via SMP domains. E-Syt1 tethers and transports lipids in a Ca2+-dependent manner, but the role of Ca2+ in this regulation is unclear. Of the five C2 domains of E-Syt1, only C2A and C2C contain Ca2+-binding sites. Using liposome-based assays, we show that Ca2+ binding to C2C promotes E-Syt1-mediated membrane tethering by releasing an inhibition that prevents C2E from interacting with PI(4,5)P2-rich membranes, as previously suggested by studies in semi-permeabilized cells...
December 8, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29217618/lps-upregulates-palmitoylated-enzymes-of-the-phosphatidylinositol-cycle-an-insight-from-proteomic-studies
#6
Justyna Sobocińska, Paula Roszczenko-Jasińska, Monika Zaręba-Kozioł, Aneta Hromada-Judycka, Orest V Matveichuk, Gabriela Traczyk, Katarzyna Łukasiuk, Katarzyna Kwiatkowska
Lipopolysaccharide (LPS) is a component of the outer membrane of Gram-negative bacteria which induces strong pro-inflammatory reactions of mammals. These processes are triggered upon sequential binding of LPS to CD14, a GPI-linked plasma membrane raft protein, and to the TLR4/MD2 receptor complex. We have found earlier that upon LPS binding CD14 triggers generation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], a lipid controlling subsequent pro-inflammatory cytokine production. Here we show that stimulation of RAW264 macrophage-like cells with LPS induces global changes of the level of fatty-acylated, most likely palmitoylated, proteins...
December 7, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29192764/light-control-of-protein-solubility-through-isoelectric-point-modulation
#7
Karthik Nadendla, Simon H Friedman
We previously described the photoactivated depot or PAD approach that allows for the light control of therapeutic protein release. This approach relies on the ability to use light to change a protein's solubility. Traditionally this was accomplished by linking the protein to an insoluble but injectable polymer via a light cleaved linker. This allows the injected material to remain at the site of injection, until transcutaneous irradiation breaks the link between polymer and protein, permitting the protein to be absorbed...
December 1, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29192062/distinct-roles-for-plasma-membrane-ptdins-4-p-and-ptdins-4-5-p2-during-yeast-receptor-mediated-endocytosis
#8
Wataru Yamamoto, Suguru Wada, Makoto Nagano, Kaito Aoshima, Daria Elisabeth Siekhaus, Junko Y Toshima, Jiro Toshima
Clathrin-mediated endocytosis requires the coordinated assembly of various endocytic proteins and lipids at the plasma membrane. Accumulating evidence demonstrates a crucial role for phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) in endocytosis, but specific roles for PtdIns(4)P other than as the biosynthetic precursor of PtdIns(4,5)P2 have not been clarified. In this study we investigated the role of PtdIns(4)P or PtdIns(4,5)P2 in receptor-mediated endocytosis through the construction of temperature-sensitive (ts) mutants for the PI 4-kinases Stt4p and Pik1p and the PtdIns(4) 5-kinase Mss4p...
November 30, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29154995/a-map-of-the-subcellular-distribution-of-phosphoinositides-in-the-erythrocytic-cycle-of-the-malaria-parasite-plasmodium-falciparum
#9
Zeinab Ebrahimzadeh, Angana Mukherjee, Dave Richard
Despite representing a small percentage of the cellular lipids of eukaryotic cells, phosphoinositides (PIPs) are critical in various processes such as intracellular trafficking and signal transduction. Central to their various functions is the differential distribution of PIP species to specific membrane compartments through the actions of kinases, phosphatases and lipases. Despite their importance in the malaria parasite lifecycle, the subcellular distribution of most PIP species in this organism is still unknown...
November 15, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/29100049/pip-ing-lipids-on-membranes-pten-takes-the-cake
#10
Archna Ravi, Brooke M Emerling
In this issue of Molecular Cell, Malek et al. (2017) describe a novel HPLC-MS method permitting separation of PI(3,4)P2 and PI(4,5)P2, a technical issue hindering the phosphoinositide signaling field. They use this method to uncover a new target and critical role for PTEN in cancer.
November 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29078297/increased-intracellular-ca2-concentrations-prevent-membrane-localization-of-ph-domains-through-the-formation-of-ca2-phosphoinositides
#11
Jin Ku Kang, Ok-Hee Kim, June Hur, So Hee Yu, Santosh Lamichhane, Jin Wook Lee, Uttam Ojha, Jeong Hee Hong, Cheol Soon Lee, Ji-Young Cha, Young Jae Lee, Seung-Soon Im, Young Joo Park, Cheol Soo Choi, Dae Ho Lee, In-Kyu Lee, Byung-Chul Oh
Insulin resistance, a key etiological factor in metabolic syndrome, is closely linked to ectopic lipid accumulation and increased intracellular Ca2+ concentrations in muscle and liver. However, the mechanism by which dysregulated intracellular Ca2+ homeostasis causes insulin resistance remains elusive. Here, we show that increased intracellular Ca2+ acts as a negative regulator of insulin signaling. Chronic intracellular Ca2+ overload in hepatocytes during obesity and hyperlipidemia attenuates the phosphorylation of protein kinase B (Akt) and its key downstream signaling molecules by inhibiting membrane localization of pleckstrin homology (PH) domains...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29073094/mechanistic-principles-underlying-regulation-of-the-actin-cytoskeleton-by-phosphoinositides
#12
Yosuke Senju, Maria Kalimeri, Essi V Koskela, Pentti Somerharju, Hongxia Zhao, Ilpo Vattulainen, Pekka Lappalainen
The actin cytoskeleton powers membrane deformation during many cellular processes, such as migration, morphogenesis, and endocytosis. Membrane phosphoinositides, especially phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], regulate the activities of many actin-binding proteins (ABPs), including profilin, cofilin, Dia2, N-WASP, ezrin, and moesin, but the underlying molecular mechanisms have remained elusive. Moreover, because of a lack of available methodology, the dynamics of membrane interactions have not been experimentally determined for any ABP...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29068313/phosphatidylinositol-4-5-bisphosphate-optical-uncaging-potentiates-exocytosis
#13
Alexander M Walter, Rainer Müller, Bassam Tawfik, Keimpe Db Wierda, Paulo S Pinheiro, André Nadler, Anthony W McCarthy, Iwona Ziomkiewicz, Martin Kruse, Gregor Reither, Jens Rettig, Martin Lehmann, Volker Haucke, Bertil Hille, Carsten Schultz, Jakob Balslev Sorensen
Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] is essential for exocytosis. Classical ways of manipulating PI(4,5)P2 levels are slower than metabolism, making it difficult to distinguish effects of PI(4,5)P2 from those of its metabolites. We developed a membrane-permeant, photoactivatable PI(4,5)P2, which is loaded into cells in an inactive form and activated by light, allowing sub-second increases in PI(4,5)P2 levels. By combining this compound with electrophysiological measurements in mouse adrenal chromaffin cells, we show that PI(4,5)P2 uncaging potentiates exocytosis and identify synaptotagmin-1 (the Ca(2+) sensor for exocytosis) and Munc13-2 (a vesicle priming protein) as the relevant effector proteins...
October 25, 2017: ELife
https://www.readbyqxmd.com/read/29056325/pten-regulates-pi-3-4-p2-signaling-downstream-of-class-i-pi3k
#14
Mouhannad Malek, Anna Kielkowska, Tamara Chessa, Karen E Anderson, David Barneda, Pınar Pir, Hiroki Nakanishi, Satoshi Eguchi, Atsushi Koizumi, Junko Sasaki, Véronique Juvin, Vladimir Y Kiselev, Izabella Niewczas, Alexander Gray, Alexandre Valayer, Dominik Spensberger, Marine Imbert, Sergio Felisbino, Tomonori Habuchi, Soren Beinke, Sabina Cosulich, Nicolas Le Novère, Takehiko Sasaki, Jonathan Clark, Phillip T Hawkins, Len R Stephens
The PI3K signaling pathway regulates cell growth and movement and is heavily mutated in cancer. Class I PI3Ks synthesize the lipid messenger PI(3,4,5)P3. PI(3,4,5)P3 can be dephosphorylated by 3- or 5-phosphatases, the latter producing PI(3,4)P2. The PTEN tumor suppressor is thought to function primarily as a PI(3,4,5)P3 3-phosphatase, limiting activation of this pathway. Here we show that PTEN also functions as a PI(3,4)P2 3-phosphatase, both in vitro and in vivo. PTEN is a major PI(3,4)P2 phosphatase in Mcf10a cytosol, and loss of PTEN and INPP4B, a known PI(3,4)P2 4-phosphatase, leads to synergistic accumulation of PI(3,4)P2, which correlated with increased invadopodia in epidermal growth factor (EGF)-stimulated cells...
November 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29020973/the-%C3%AE-melanocyte-stimulating-hormone-peroxisome-proliferator-activated-receptor-%C3%AE-pathway-down-regulates-proliferation-in-melanoma-cell-lines
#15
Enrica Flori, Eleonora Rosati, Giorgia Cardinali, Daniela Kovacs, Barbara Bellei, Mauro Picardo, Vittoria Maresca
BACKGROUND: The α-Melanocyte Stimulating Hormone (αMSH)/Melanocortin-1 receptor (MC1R) interaction promotes melanogenesis through the cAMP/PKA pathway. The direct induction of this pathway by Forskolin (FSK) is also known to enhance melanocyte proliferation. αMSH acts as a mitogenic agent in melanocytes and its effect on proliferation of melanoma cells is less known. We previously identified the αMSH/Peroxisome Proliferator Activated Receptor (PPARγ) pathway as a new pathway on the B16-F10 mouse melanoma cell line...
October 11, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28993456/phosphatidylinositol-4-5-bisphosphate-dependent-oligomerization-of-the-pseudomonas-aeruginosa-cytotoxin-exou
#16
Angelica Zhang, Jeffrey L Veesenmeyer, Alan R Hauser
The Pseudomonas aeruginosa type III secretion system delivers effector proteins directly into target cells, allowing the bacterium to modulate host cell functions. ExoU is the most cytotoxic of the known effector proteins and has been associated with more severe infections in humans. ExoU is a patatin-like A2 phospholipase requiring the cellular host factors phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and ubiquitin for its activation in vitro We demonstrated that PI(4,5)P2 also induces oligomerization of ExoU and that this PI(4,5)P2-mediated oligomerization does not require ubiquitin...
October 9, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28988317/identification-of-critical-amino-acids-in-the-proximal-c-terminal-of-trek-2-k-channel-for-activation-by-acidic-phi-and-atp-dependent-inhibition
#17
Joohan Woo, Young Keul Jun, Yin-Hua Zhang, Joo Hyun Nam, Dong Hoon Shin, Sung Joon Kim
TWIK-related two-pore domain K(+) channels (TREKs) are regulated by intracellular pH (pHi) and Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). Previously, Glu(306) in proximal C-terminal (pCt) of mouse TREK-1 was identified as the pHi-sensing residue. The direction of PI(4,5)P2 sensitivity is controversial, and we have recently shown that TREKs are inhibited by intracellular ATP via endogenous PI(4,5)P2 formation. Here we investigate the anionic and cationic residues of pCt for the pHi and ATP-sensitivity in human TREK-2 (hTREK-2)...
October 8, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28970821/hpv8-e6-interferes-with-syntenin-2-expression-through-deregulation-of-differentiation-methylation-and-phosphatidylinositide-kinase-dependent-mechanisms
#18
Benjamin Marx, Daliborka Miller-Lazic, John Doorbar, Slawomir Majewski, Kay Hofmann, Martin Hufbauer, Baki Akgül
The E6 oncoproteins of high-risk human papillomaviruses (HPV) of genus alpha contain a short peptide sequence at the carboxy-terminus, the PDZ binding domain, with which they interact with the corresponding PDZ domain of cellular proteins. Interestingly, E6 proteins from papillomaviruses of genus beta (betaPV) do not encode a comparable PDZ binding domain. Irrespective of this fact, we previously showed that the E6 protein of HPV8 (betaPV type) could circumvent this deficit by targeting the PDZ protein Syntenin-2 through transcriptional repression (Lazic et al...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28961003/membrane-order-is-a-key-regulator-of-divalent-cation-induced-clustering-of-pi-3-5-p2-and-pi-4-5-p2
#19
Maria J Sarmento, Ana Coutinho, Aleksander Fedorov, Manuel Prieto, Fábio Fernandes
Although the evidence for the presence of functionally important nanosized phosphorylated phosphoinositide (PIP)-rich domains within cellular membranes has accumulated, very limited information is available regarding the structural determinants for compartmentalization of these phospholipids. Here, we used a combination of fluorescence spectroscopy and microscopy techniques to characterize differences in divalent cation-induced clustering of PI(4,5)P2 and PI(3,5)P2. Through these methodologies we were able to detect differences in divalent cation-induced clustering efficiency and cluster size...
October 13, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28954864/cortical-actin-contributes-to-spatial-organization-of-er-pm-junctions
#20
Ting-Sung Hsieh, Yu-Ju Chen, Chi-Lun Chang, Wan-Ru Lee, Jen Liou
Endoplasmic reticulum-plasma membrane (ER-PM) junctions mediate crucial activities ranging from Ca(2+) signaling to lipid metabolism. Spatial organization of ER-PM junctions may modulate the extent and location of these cellular activities. However, the morphology and distribution of ER-PM junctions are not well characterized. Using photoactivated localization microscopy, we reveal that the contact area of single ER-PM junctions is mainly oblong with the dimensions of ∼120 nm × ∼80 nm in HeLa cells. Using total internal reflection fluorescence microscopy and structure illumination microscopy, we show that cortical actin contributes to spatial distribution and stability of ER-PM junctions...
November 7, 2017: Molecular Biology of the Cell
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