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https://www.readbyqxmd.com/read/29186690/growth-of-b-cell-receptor-microclusters-is-regulated-by-pip2-and-pip3-equilibrium-and-dock2-recruitment-and-activation
#1
Jing Wang, Liling Xu, Samina Shaheen, Sichen Liu, Wenjie Zheng, Xiaolin Sun, Zhanguo Li, Wanli Liu
The growth of B cell receptor (BCR) microclusters upon antigen stimulation drives B cell activation. Here, we show that PI3K-mediated PIP3 production is required for the growth of BCR microclusters. This growth is likely inhibited by PTEN and dependent on its plasma membrane binding and lipid phosphatase activities. Mechanistically, we find that PIP3-dependent recruitment and activation of a guanine nucleotide exchange factor, Dock2, is required for the sustained growth of BCR microclusters through remodeling of the F-actin cytoskeleton...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29141223/gradients-of-rac1-nanoclusters-support-spatial-patterns-of-rac1-signaling
#2
Amanda Remorino, Simon De Beco, Fanny Cayrac, Fahima Di Federico, Gaetan Cornilleau, Alexis Gautreau, Maria Carla Parrini, Jean-Baptiste Masson, Maxime Dahan, Mathieu Coppey
Rac1 is a small RhoGTPase switch that orchestrates actin branching in space and time and protrusion/retraction cycles of the lamellipodia at the cell front during mesenchymal migration. Biosensor imaging has revealed a graded concentration of active GTP-loaded Rac1 in protruding regions of the cell. Here, using single-molecule imaging and super-resolution microscopy, we show an additional supramolecular organization of Rac1. We find that Rac1 partitions and is immobilized into nanoclusters of 50-100 molecules each...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29122926/defect-in-phosphoinositide-signalling-through-a-homozygous-variant-in-plcb3-causes-a-new-form-of-spondylometaphyseal-dysplasia-with-corneal-dystrophy
#3
Salma Ben-Salem, Sarah M Robbins, Nara Lm Sobreira, Angeline Lyon, Aisha M Al-Shamsi, Barira K Islam, Nadia A Akawi, Anne John, Pramathan Thachillath, Sania Al Hamed, David Valle, Bassam R Ali, Lihadh Al-Gazali
BACKGROUND: Bone dysplasias are a large group of disorders affecting the growth and structure of the skeletal system. METHODS: In the present study, we report the clinical and molecular delineation of a new form of syndromic autosomal recessive spondylometaphyseal dysplasia (SMD) in two Emirati first cousins. They displayed postnatal growth deficiency causing profound limb shortening with proximal and distal segments involvement, narrow chest, radiological abnormalities involving the spine, pelvis and metaphyses, corneal clouding and intellectual disability...
November 9, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29034471/lipid-signaling-affects-primary-fibroblast-collective-migration-and-anchorage-in-response-to-stiffness-and-microtopography
#4
Michael A Mkrtschjan, Snehal B Gaikwad, Kevin J Kappenman, Christopher Solís, Sagar Dommaraju, Long Le, Tejal A Desai, Brenda Russell
Cell migration is regulated by several mechanotransduction pathways, which consist of sensing and converting mechanical microenvironmental cues to internal biochemical cellular signals, such as protein phosphorylation and lipid signaling. While there has been significant progress in understanding protein changes in the context of mechanotransduction, lipid signaling is more difficult to investigate. In this study, physical cues of stiffness (10 kPa, 100 kPa, 400 kPa, and glass), and microrod or micropost topography were manipulated in order to reprogram primary fibroblasts and assess the effects of lipid signaling on the actin cytoskeleton...
October 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28955986/nspef-induced-pip2-depletion-plc-activity-and-actin-cytoskeletal-cortex-remodeling-are-responsible-for-post-exposure-cellular-swelling-and-blebbing
#5
Gleb P Tolstykh, Gary L Thompson, Hope T Beier, Zachary A Steelman, Bennett L Ibey
Cell swelling and blebbing has been commonly observed following nanosecond pulsed electric field (nsPEF) exposure. The hypothesized origin of these effects is nanoporation of the plasma membrane (PM) followed by transmembrane diffusion of extracellular fluid and disassembly of cortical actin structures. This investigation will provide evidence that shows passive movement of fluid into the cell through nanopores and increase of intracellular osmotic pressure are not solely responsible for this observed phenomena...
March 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28716933/cortical-actin-recovery-at-the-immunological-synapse-leads-to-termination-of-lytic-granule-secretion-in-cytotoxic-t-lymphocytes
#6
Alex T Ritter, Senta M Kapnick, Sricharan Murugesan, Pamela L Schwartzberg, Gillian M Griffiths, Jennifer Lippincott-Schwartz
CD8(+) cytotoxic T lymphocytes (CTLs) eliminate virally infected cells through directed secretion of specialized lytic granules. Because a single CTL can kill multiple targets, degranulation must be tightly regulated. However, how CTLs regulate the termination of granule secretion remains unclear. Previous work demonstrated that centralized actin reduction at the immune synapse precedes degranulation. Using a combination of live confocal, total internal reflection fluorescence, and superresolution microscopy, we now show that, after granule fusion, actin recovers at the synapse and no further secretion is observed...
August 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28680082/visualizing-temperature-mediated-activation-of-gelsolin-and-its-deactivation-by-pip2-a-saxs-based-study
#7
Maulik D Badmalia, Shikha Singh, Renu Garg, Ashish
This is the first report describing temperature based initiation of gelsolin's F-actin depolymerization activity, even in absence of free Ca(2+) or low pH. Small angle X-ray scattering (SAXS) and circular dichroism (CD) studies revealed that temperature in the range of 30-40 °C is capable of opening the G1 domain alone, as remaining domains are held together by the Ca(2+)-sensitive C-tail latch without any loss in the secondary structural content. Full opening of all domains of tail-less gelsolin, and retention of closed shape for G2-G6 gelsolin merely by heating, further substantiated our findings...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28606474/regulation-of-intracellular-trafficking-and-secretion-of-adiponectin-by-myosin-ii
#8
Deepa Bedi, John C Dennis, Edward E Morrison, Tim D Braden, Robert L Judd
Adiponectin is a protein secreted by white adipocytes that plays an important role in insulin action, energy homeostasis and the development of atherosclerosis. The intracellular localization and trafficking of GLUT4 and leptin in adipocytes has been well studied, but little is known regarding the intracellular trafficking of adiponectin. Recent studies have demonstrated that constitutive adiponectin secretion is dependent on PIP2 levels and the integrity of cortical F-actin. Non-muscle myosin II is an actin-based motor that is associated with membrane vesicles and participates in vesicular trafficking in mammalian cells...
August 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28542408/mocap-proteins-regulated-by-moark1-mediated-phosphorylation-coordinate-endocytosis-and-actin-dynamics-to-govern-development-and-virulence-of-magnaporthe-oryzae
#9
Lianwei Li, Xiaolin Chen, Shengpei Zhang, Jun Yang, Deng Chen, Muxing Liu, Haifeng Zhang, Xiaobo Zheng, Ping Wang, Youliang Peng, Zhengguang Zhang
Actin organization is a conserved cellular process that regulates the growth and development of eukaryotic cells. It also governs the virulence process of pathogenic fungi, such as the rice blast fungus Magnaporthe oryzae, with mechanisms not yet fully understood. In a previous study, we found that actin-regulating kinase MoArk1 displays conserved functions important in endocytosis and actin organization, and MoArk1 is required for maintaining the growth and full virulence of M. oryzae. To understand how MoArk1 might function, we identified capping protein homologs from M...
May 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28533957/pld2-regulates-microtubule-stability-and-spindle-migration-in-mouse-oocytes-during-meiotic-division
#10
Xiaoyu Liu, Xiaoyun Liu, Dandan Chen, Xiuying Jiang, Wei Ma
Phospholipase D2 (PLD2) is involved in cytoskeletal reorganization, cell migration, cell cycle progression, transcriptional control and vesicle trafficking. There is no evidence about PLD2 function in oocytes during meiosis. Herein, we analyzed PLD2 expression and its relationship with spindle formation and positioning in mouse oocyte meiosis. High protein level of PLD2 was revealed in oocytes by Western blot, which remained consistently stable from prophase I with intact germinal vesicle (GV) up to metaphase II (MII) stage...
2017: PeerJ
https://www.readbyqxmd.com/read/28430576/ezrin-activation-by-lok-phosphorylation-involves-a-pip2-dependent-wedge-mechanism
#11
Thaher Pelaseyed, Cécile Sauvanet, Raghuvir Viswanatha, Joshua J Filter, Michael L Goldberg, Anthony Bretscher
How cells specify morphologically distinct plasma membrane domains is poorly understood. Prior work has shown that restriction of microvilli to the apical aspect of epithelial cells requires the localized activation of the membrane-F-actin linking protein ezrin. Using an in vitro system, we now define a multi-step process whereby the kinase LOK specifically phosphorylates ezrin to activate it. Binding of PIP2 to ezrin induces a conformational change permitting the insertion of the LOK C-terminal domain to wedge apart the membrane and F-actin-binding domains of ezrin...
April 21, 2017: ELife
https://www.readbyqxmd.com/read/28400525/manipulation-of-the-host-cell-membrane-during-plasmodium-liver-stage-egress
#12
Paul-Christian Burda, Reto Caldelari, Volker T Heussler
A crucial step in the life cycle of Plasmodium parasites is the transition from the liver stage to the blood stage. Hepatocyte-derived merozoites reach the blood vessels of the liver inside host cell-derived vesicles called merosomes. The molecular basis of merosome formation is only partially understood. Here we show that Plasmodium berghei liver stage merozoites, upon rupture of the parasitophorous vacuole membrane, destabilize the host cell membrane (HCM) and induce separation of the host cell actin cytoskeleton from the HCM...
April 11, 2017: MBio
https://www.readbyqxmd.com/read/28118027/impaired-relaxation-of-airway-smooth-muscle-in-mice-lacking-the-actin-binding-protein-gelsolin
#13
Maya Mikami, Yi Zhang, Jennifer Danielsson, Tiarra Joell, Hwan Mee Yong, Elizabeth Townsend, Seema Khurana, Steven S An, Charles W Emala
Diverse classes of ligands have recently been discovered that relax airway smooth muscle (ASM) despite a transient increase in intracellular calcium concentrations ([Ca(2+)]i). However, the cellular mechanisms are not well understood. Gelsolin is a calcium-activated actin-severing and -capping protein found in many cell types, including ASM cells. Gelsolin also binds to phosphatidylinositol 4,5-bisphosphate, making this substrate less available for phospholipase Cβ-mediated hydrolysis to inositol triphosphate and diacylglycerol...
May 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28089450/a-structural-model-for-vinculin-insertion-into-pip2-containing-membranes-and-the-effect-of-insertion-on-vinculin-activation-and-localization
#14
Peter M Thompson, Srinivas Ramachandran, Lindsay B Case, Caitlin E Tolbert, Arpit Tandon, Mihir Pershad, Nikolay V Dokholyan, Clare M Waterman, Sharon L Campbell
Vinculin, a scaffolding protein that localizes to focal adhesions (FAs) and adherens junctions, links the actin cytoskeleton to the adhesive super-structure. While vinculin binds to a number of cytoskeletal proteins, it can also associate with phosphatidylinositol 4,5-bisphosphate (PIP2) to drive membrane association. To generate a structural model for PIP2-dependent interaction of vinculin with the lipid bilayer, we conducted lipid-association, nuclear magnetic resonance, and computational modeling experiments...
February 7, 2017: Structure
https://www.readbyqxmd.com/read/27933776/regulation-of-a-coupled-marcks-pi3k-lipid-kinase-circuit-by-calmodulin-single-molecule-analysis-of-a-membrane-bound-signaling-module
#15
Brian P Ziemba, G Hayden Swisher, Glenn Masson, John E Burke, Roger L Williams, Joseph J Falke
Amoeboid cells that employ chemotaxis to travel up an attractant gradient possess a signaling network assembled on the leading edge of the plasma membrane that senses the gradient and remodels the actin mesh and cell membrane to drive movement in the appropriate direction. In leukocytes such as macrophages and neutrophils, and perhaps in other amoeboid cells as well, the leading edge network includes a positive feedback loop in which the signaling of multiple pathway components is cooperatively coupled. Cytoplasmic Ca(2+) is a recently recognized component of the feedback loop at the leading edge where it stimulates phosphoinositide-3-kinase (PI3K) and the production of its product signaling lipid phosphatidylinositol 3,4,5-trisphosphate (PIP3)...
November 22, 2016: Biochemistry
https://www.readbyqxmd.com/read/27627778/gelsolin-in-onychophora-and-tardigrada-with-notes-on-its-variability-in-the-ecdysozoa
#16
Prasath Thiruketheeswaran, Hartmut Greven, Jochen D'Haese
Rearrangements of the filamentous actin network involve a broad range of actin binding proteins. Among these, the gelsolin proteins sever actin filaments, cap their fast growing end and nucleate actin assembly in a calcium-dependent manner. Here, we focus on the gelsolin of the onychophoran Peripatoides novaezealandiae and the eutardigrade Hypsibius dujardini. From the cDNA of P. novaezealandiae we obtained the complete coding sequence with an open reading frame of 2178bp. It encodes a protein of 726 amino acids with a calculated molecular mass of 82,610...
January 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/27486838/variation-in-stiffness-regulates-cardiac-myocyte-hypertrophy-via-signaling-pathways
#17
Jieli Li, Michael A Mkrtschjan, Ying-Hsi Lin, Brenda Russell
Much diseased human myocardial tissue is fibrotic and stiff, which increases the work that the ventricular myocytes must perform to maintain cardiac output. The hypothesis tested is that the increased load due to greater stiffness of the substrata drives sarcomere assembly of cells, thus strengthening them. Neonatal rat ventricular myocytes (NRVM) were cultured on polyacrylamide or polydimethylsiloxane substrates with stiffness of 10 kPa, 100 kPa, or 400 kPa, or glass with stiffness of 61.9 GPa. Cell size increased with stiffness...
June 15, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27242793/phosphatidylinositol-4-phosphate-5-kinases-in-the-regulation-of-t-cell-activation
#18
REVIEW
Nicla Porciello, Martina Kunkl, Antonella Viola, Loretta Tuosto
Phosphatidylinositol 4,5-biphosphate kinases (PIP5Ks) are critical regulators of T cell activation being the main enzymes involved in the synthesis of phosphatidylinositol 4,5-biphosphate (PIP2). PIP2 is indeed a pivotal regulator of the actin cytoskeleton, thus controlling T cell polarization and migration, stable adhesion to antigen-presenting cells, spatial organization of the immunological synapse, and co-stimulation. Moreover, PIP2 also serves as a precursor for the second messengers inositol triphosphate, diacylglycerol, and phosphatidylinositol 3,4,5-triphosphate, which are essential for the activation of signaling pathways regulating cytokine production, cell cycle progression, survival, metabolism, and differentiation...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27224309/cholesterol-dependent-phase-demixing-in-lipid-bilayers-as-a-switch-for-the-activity-of-the-phosphoinositide-binding-cytoskeletal-protein-gelsolin
#19
Yu-Hsiu Wang, Robert Bucki, Paul A Janmey
The lateral distribution of phosphatidylinositol 4,5-bisphosphate (PIP2) in lipid bilayers is affected both by divalent cation-mediated attractions and cholesterol-dependent phase demixing. The effects of lateral redistribution of PIP2 within a membrane on PIP2-protein interactions are explored with an N-terminal fragment of gelsolin (NtGSN) that severs actin in a Ca(2+)-insensitive manner. The extent of NtGSN inhibition by PIP2-containing large unilamellar vesicles (LUVs) depends on the lateral organization of the membrane as quantified by an actin-severing assay...
June 21, 2016: Biochemistry
https://www.readbyqxmd.com/read/27119641/regulation-of-pi3k-by-pkc-and-marcks-single-molecule-analysis-of-a-reconstituted-signaling-pathway
#20
Brian P Ziemba, John E Burke, Glenn Masson, Roger L Williams, Joseph J Falke
In chemotaxing ameboid cells, a complex leading-edge signaling circuit forms on the cytoplasmic leaflet of the plasma membrane and directs both actin and membrane remodeling to propel the leading edge up an attractant gradient. This leading-edge circuit includes a putative amplification module in which Ca(2+)-protein kinase C (Ca(2+)-PKC) is hypothesized to phosphorylate myristoylated alanine-rich C kinase substrate (MARCKS) and release phosphatidylinositol-4,5-bisphosphate (PIP2), thereby stimulating production of the signaling lipid phosphatidylinositol-3,4,5-trisphosphate (PIP3) by the lipid kinase phosphoinositide-3-kinase (PI3K)...
April 26, 2016: Biophysical Journal
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