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https://www.readbyqxmd.com/read/29891700/hiv-1-gag-recruits-pacsin2-to-promote-virus-spreading
#1
Sergei Popov, Elena Popova, Michio Inoue, Yuanfei Wu, Heinrich Göttlinger
The p2b domain of Rous sarcoma virus (RSV) Gag and the p6 domain of HIV-1 Gag contain late assembly (L) domains that engage the ESCRT membrane fission machinery and are essential for virus release. We now show that the PPXY-type RSV L domain specifically recruits the BAR domain protein PACSIN2 into virus-like particles (VLP), in addition to the NEDD4-like ubiquitin ligase ITCH and ESCRT pathway components such as TSG101. PACSIN2, which has been implicated in the remodeling of cellular membranes and the actin cytoskeleton, is also recruited by HIV-1 p6 independent of its ability to engage the ESCRT factors TSG101 or ALIX...
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29887380/a-flat-bar-protein-promotes-actin-polymerization-at-the-base-of-clathrin-coated-pits
#2
Leonardo Almeida-Souza, Rene A W Frank, Javier García-Nafría, Adeline Colussi, Nushan Gunawardana, Christopher M Johnson, Minmin Yu, Gillian Howard, Byron Andrews, Yvonne Vallis, Harvey T McMahon
Multiple proteins act co-operatively in mammalian clathrin-mediated endocytosis (CME) to generate endocytic vesicles from the plasma membrane. The principles controlling the activation and organization of the actin cytoskeleton during mammalian CME are, however, not fully understood. Here, we show that the protein FCHSD2 is a major activator of actin polymerization during CME. FCHSD2 deletion leads to decreased ligand uptake caused by slowed pit maturation. FCHSD2 is recruited to endocytic pits by the scaffold protein intersectin via an unusual SH3-SH3 interaction...
June 4, 2018: Cell
https://www.readbyqxmd.com/read/29785947/-n-wasp-regulates-cortical-neuron-migration-through-its-polypro-and-vca-domains
#3
Xiu Lian Shen, Yi Chao Lu, Zhi Lian Jia, Qiang Wu
Cortical neuron migration in the developing mouse forebrain is a complex process, which contains several steps related to cytoskeleton dynamics and remodeling. Neural Wiskott-Aldrich syndrome protein (N-WASP), a member of the WASP-WAVE family, regulates actin cytoskeleton reorganization through the binding of its VCA domain to the Arp2/3 complex. Here we report expression patterns of N-WASP gene in the mouse developing embryonic cortex (E12.5~ E18.5) and find its expression levels are decreased during embryonic development...
May 20, 2018: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/29755929/high-pinch1-expression-in-human-laryngeal-carcinoma-associates-with-poor-prognosis
#4
Georgios Tsinias, Sofia Nikou, Theodoros Papadas, Panagiotis Pitsos, Helen Papadaki, Vasiliki Bravou
Focal adhesion signaling to actin cytoskeleton is critically implicated in cell migration and cancer invasion and metastasis. Actin-binding proteins cofilin and N-WASP regulate actin filament turnover, and focal adhesion proteins parvins and PINCH mediate integrin signaling to the actin cytoskeleton. Altered expression of these proteins has been implicated in human cancer. This study addresses their expression and prognostic significance in human laryngeal carcinoma. Protein expressions of cofilin, N-WASP, α -parvin, β -parvin, and PINCH1 were examined by immunohistochemistry in 72 human laryngeal squamous cell carcinomas...
2018: Analytical Cellular Pathology (Amsterdam)
https://www.readbyqxmd.com/read/29746010/rho-kinase-rock-collaborates-with-pak-to-regulate-actin-polymerization-and-contraction-in-airway-smooth-muscle
#5
Wenwu Zhang, Bhupal P Bhetwal, Susan J Gunst
KEY POINTS: The mechanisms by which Rho kinase (ROCK) regulates airway smooth muscle contraction were determined in tracheal smooth muscle tissues. ROCK may mediate smooth muscle contraction by inhibiting myosin regulatory light chain (RLC) phosphatase. ROCK can also regulate F-actin dynamics during cell migration, and actin polymerization is critical for airway smooth muscle contraction. Our results show that ROCK does not regulate airway smooth muscle contraction by inhibiting myosin RLC phosphatase or by stimulating myosin RLC phosphorylation...
May 10, 2018: Journal of Physiology
https://www.readbyqxmd.com/read/29743821/blockade-of-itga2-induces-apoptosis-and-inhibits-cell-migration-in-gastric-cancer
#6
Yu-Chang Chuang, Hsin-Yi Wu, Yu-Ling Lin, Shey-Cherng Tzou, Cheng-Hsun Chuang, Ting-Yan Jian, Pin-Rong Chen, Yuan-Ching Chang, Chi-Hsin Lin, Tse-Hung Huang, Chao-Ching Wang, Yi-Lin Chan, Kuang-Wen Liao
Background: Gastric cancer is currently the fourth leading cause of cancer-related death worldwide. Gastric cancer is often diagnosed at advanced stages and the outcome of the treatment is often poor. Therefore, identifying new therapeutic targets for this cancer is urgently needed. Integrin alpha 2 (ITGA2) subunit and the beta 1 subunit form a heterodimer for a transmembrane receptor for extracellular matrix, is an important molecule involved in tumor cell proliferation, survival and migration...
2018: Biological Procedures Online
https://www.readbyqxmd.com/read/29727463/chlamydia-exploits-filopodial-capture-and-a-macropinocytosis-like-pathway-for-host-cell-entry
#7
Charlotte Ford, Andrea Nans, Emmanuel Boucrot, Richard D Hayward
Pathogens hijack host endocytic pathways to force their own entry into eukaryotic target cells. Many bacteria either exploit receptor-mediated zippering or inject virulence proteins directly to trigger membrane reorganisation and cytoskeletal rearrangements. By contrast, extracellular C. trachomatis elementary bodies (EBs) apparently employ facets of both the zipper and trigger mechanisms and are only ~400 nm in diameter. Our cryo-electron tomography of C. trachomatis entry revealed an unexpectedly diverse array of host structures in association with invading EBs, suggesting internalisation may progress by multiple, potentially redundant routes or several sequential events within a single pathway...
May 4, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29678956/local-actin-polymerization-during-endocytic-carrier-formation
#8
REVIEW
Claudia Hinze, Emmanuel Boucrot
Extracellular macromolecules, pathogens and cell surface proteins rely on endocytosis to enter cells. Key steps of endocytic carrier formation are cargo molecule selection, plasma membrane folding and detachment from the cell surface. While dedicated proteins mediate each step, the actin cytoskeleton contributes to all. However, its role can be indirect to the actual molecular events driving endocytosis. Here, we review our understanding of the molecular steps mediating local actin polymerization during the formation of endocytic carriers...
April 20, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29675452/attaching-and-effacing-pathogens-exploit-junction-regulatory-activities-of-n-wasp-and-snx9-to-disrupt-the-intestinal-barrier
#9
John J Garber, Emily M Mallick, Karen M Scanlon, Jerrold R Turner, Michael S Donnenberg, John M Leong, Scott B Snapper
Background & Aims: Neural Wiskott-Aldrich Syndrome protein (N-WASP) is a key regulator of the actin cytoskeleton in epithelial tissues and is poised to mediate cytoskeletal-dependent aspects of apical junction complex (AJC) homeostasis. Attaching-and-effacing (AE) pathogens disrupt this homeostasis through translocation of the effector molecule early secreted antigenic target-6 (ESX)-1 secretion-associated protein F (EspF). Although the mechanisms underlying AJC disruption by EspF are unknown, EspF contains putative binding sites for N-WASP and the endocytic regulator sorting nexin 9 (SNX9)...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29672847/loss-of-n-wasp-drives-early-progression-in-an-apc-model-of-intestinal-tumourigenesis
#10
Hayley T Morris, Loic Fort, Heather J Spence, Rachana Patel, David F Vincent, James H Park, Scott B Snapper, Francis A Carey, Owen J Sansom, Laura M Machesky
N-WASP (WASL) is a widely expressed cytoskeletal signalling and scaffold protein also implicated in regulation of Wnt signalling and homeostatic maintenance of skin epithelial architecture. N-WASP mediates invasion of cancer cells in vitro and its depletion reduces invasion and metastatic dissemination of breast cancer. Given this role in cancer invasion and universal expression in the gastrointestinal tract, we explored a role for N-WASP in the initiation and progression of colorectal cancer. While deletion of N-wasp is not detectably harmful in the murine intestinal tract, numbers of Paneth cells increased, indicating potential changes in the stem cell niche, and migration up the crypt-villus axis was enhanced...
April 19, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29650963/epigenetic-control-of-il-23-expression-in-keratinocytes-is-important-for-chronic-skin-inflammation
#11
Hui Li, Qi Yao, Alberto Garcia Mariscal, Xudong Wu, Justus Hülse, Esben Pedersen, Kristian Helin, Ari Waisman, Caroline Vinkel, Simon Francis Thomsen, Alexandra Avgustinova, Salvador Aznar Benitah, Paola Lovato, Hanne Norsgaard, Mette Sidsel Mortensen, Lone Veng, Björn Rozell, Cord Brakebusch
The chronic skin inflammation psoriasis is crucially dependent on the IL-23/IL-17 cytokine axis. Although IL-23 is expressed by psoriatic keratinocytes and immune cells, only the immune cell-derived IL-23 is believed to be disease relevant. Here we use a genetic mouse model to show that keratinocyte-produced IL-23 is sufficient to cause a chronic skin inflammation with an IL-17 profile. Furthermore, we reveal a cell-autonomous nuclear function for the actin polymerizing molecule N-WASP, which controls IL-23 expression in keratinocytes by regulating the degradation of the histone methyltransferases G9a and GLP, and H3K9 dimethylation of the IL-23 promoter...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29621773/microrna-214-5p-inhibits-the-invasion-and-migration-of-hepatocellular-carcinoma-cells-by-targeting-wiskott-aldrich-syndrome-like
#12
Hongdan Li, Haoqi Wang, Zhen Ren
BACKGROUND/AIMS: This study aims to explore the effects of microRNA-214-5p (miR-214-5p) on the invasion and migration of Hepatocellular Carcinoma cells (HCC). METHODS: Hepatocellular Carcinoma tissues and adjacent normal tissues from 44 hepatocellular carcinoma patients were prepared for this study. The HepG2 and BEL-7402 cells were transfected with miR-214-5p mimic and inhibitor. qRT-PCR was performed to detect the expressions of miR-214-5p. Transwell assays were used to detect the invasion and migration assays in HepG2 and BEL-7402 cells...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29541069/rac1-wave2-and-cdc42-n-wasp-participation-in-actin-dependent-host-cell-invasion-by-extracellular-amastigotes-of-trypanosoma-cruzi
#13
Alexis Bonfim-Melo, Éden R Ferreira, Renato A Mortara
This study evaluated the participation of host cell Rho-family GTPases and their effector proteins in the actin-dependent invasion by Trypanosoma cruzi extracellular amastigotes (EAs). We observed that all proteins were recruited and colocalized with actin at EA invasion sites in live or fixed cells. EA internalization was inhibited in cells depleted in Rac1, N-WASP, and WAVE2. Time-lapse experiments with Rac1, N-WASP and WAVE2 depleted cells revealed that EA internalization kinetics is delayed even though no differences were observed in the proportion of EA-induced actin recruitment in these groups...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29470947/small-and-large-intestine-express-a-truncated-dab1-isoform-that-assembles-in-cell-cell-junctions-and-co-localizes-with-proteins-involved-in-endocytosis
#14
María D Vázquez-Carretero, Pablo García-Miranda, María S Balda, Karl Matter, María J Peral, Anunciación A Ilundain
Disabled-1 (Dab1) is an essential intracellular adaptor protein in the reelin pathway. Our previous studies in mice intestine showed that Dab1 transmits the reelin signal to cytosolic signalling pathways. Here, we determine the Dab1 isoform expressed in rodent small and large intestine, its subcellular location and co-localization with clathrin, caveolin-1 and N-Wasp. PCR and sequencing analysis reveal that rodent small and large intestine express a Dab1 isoform that misses three (Y198 , Y200 and Y220 ) of the five tyrosine phosphorylation sites present in brain Dab1 isoform (canonical) and contains nuclear localization and export signals...
February 19, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29382077/vegf-triggers-the-activation-of-cofilin-and-the-arp2-3-complex-within-the-growth-cone
#15
Matthias Schlau, Daniel Terheyden-Keighley, Verena Theis, Hans Georg Mannherz, Carsten Theiss
A crucial neuronal structure for the development and regeneration of neuronal networks is the axonal growth cone. Affected by different guidance cues, it grows in a predetermined direction to reach its final destination. One of those cues is the vascular endothelial growth factor (VEGF), which was identified as a positive effector for growth cone movement. These positive effects are mainly mediated by a reorganization of the actin network. This study shows that VEGF triggers a tight colocalization of cofilin and the Arp2/3 complex to the actin cytoskeleton within chicken dorsal root ganglia (DRG)...
January 27, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29288926/efhd2-swiprosin-1-regulates-lps-induced-macrophage-recruitment-via-enhancing-actin-polymerization-and-cell-migration
#16
Ye Tu, Lichao Zhang, Lingchang Tong, Yue Wang, Su Zhang, Rongmei Wang, Ling Li, Zhibin Wang
Macrophage motility is vital in innate immunity, which contributes strategically to the defensive inflammation process. During bacterial infection, lipopolysaccharide (LPS) potently activates the migration of macrophages via the NF-κB/iNOS/c-Src signaling pathway. However, the downstream region of c-Src that participates in macrophage migration is unclear. EFhd2, a novel actin bundling protein, was evaluated for its role in LPS-stimulated macrophage migration in this study. We found that LPS stimulated the up-regulation, tyrosine phosphorylation and membrane translocation of EFhd2 in macrophages...
February 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29190677/cortical-actin-nodes-their-dynamics-and-recruitment-of-podosomal-proteins-as-revealed-by-super-resolution-and-single-molecule-microscopy
#17
Yuki M Shirai, Taka A Tsunoyama, Nao Hiramoto-Yamaki, Koichiro M Hirosawa, Akihiro C E Shibata, Kenichi Kondo, Atsushi Tsurumune, Fumiyoshi Ishidate, Akihiro Kusumi, Takahiro K Fujiwara
Electron tomography of the plasma membrane (PM) identified several layers of cortical actin meshwork running parallel to the PM cytoplasmic surface throughout the PM. Here, cortical actin structures and dynamics were examined in living cells, using super-resolution microscopy, with (x,y)- and z-resolutions of ~140 and ~400 nm, respectively, and single-molecule imaging. The super-resolution microscopy identified sub-micron-sized actin clusters that appeared identical by both phalloidin post-fixation staining and Lifeact-mGFP expression followed by fixation, and therefore, these actin clusters were named "actin-pl-clusters"...
2017: PloS One
https://www.readbyqxmd.com/read/29179463/olaquindox-disrupts-tight-junction-integrity-and-cytoskeleton-architecture-in-mouse-sertoli-cells
#18
Di Wu, Chun-Jie Huang, Xiao-Fei Jiao, Zhi-Ming Ding, Jia-Yu Zhang, Fan Chen, Yong-Sheng Wang, Xiang Li, Li-Jun Huo
Sertoli cells, by creating an immune-privileged and nutrition supporting environment, maintain mammalian spermatogenesis and thereby holds the heart of male fertility. Olaquindox, an effective feed additive in livestock industry, could potentially expose human into the risk of biological hazards due to its genotoxicity and cytotoxicity, highlighting the significance of determining its bio-safety regarding human reproduction. Herein, we deciphered the detrimental effects of olaquindox on male fertility by mechanistically unraveling how olaquindox intervenes blood-testis barrier in mouse...
October 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/29172947/crosstalk-between-wip-and-rho-family-gtpases
#19
Inés M Antón, Carla Gómez-Oro, Sergio Rivas, Francisco Wandosell
Through actin-binding proteins such as the neural Wiskott-Aldrich syndrome protein (N-WASP) and WASP-interacting protein (WIP), the Rho family GTPases RhoA, Rac1 and Cdc42 are major modulators of the cytoskeleton. (N-)WASP and WIP control Rho GTPase activity in various cell types, either by direct WIP/(N-)WASP/Cdc42 or potential WIP/RhoA binding, or through secondary links that regulate GTPase distribution and/or transcription levels. WIP helps to regulate filopodium generation and participates in the Rac1-mediated ruffle formation that determines cell motility...
January 29, 2018: Small GTPases
https://www.readbyqxmd.com/read/29161594/clathrin-assembly-defines-the-onset-and-geometry-of-cortical-patterning
#20
Yang Yang, Ding Xiong, Anne Pipathsouk, Orion D Weiner, Min Wu
Assembly of the endocytic machinery is a constitutively active process that is important for the organization of the plasma membrane, signal transduction, and membrane trafficking. Existing research has focused on the stochastic nature of endocytosis. Here, we report the emergence of the collective dynamics of endocytic proteins as periodic traveling waves on the cell surface. Coordinated clathrin assembly provides the earliest spatial cue for cortical waves and sets the direction of propagation. Surprisingly, the onset of clathrin waves, but not individual endocytic events, requires feedback from downstream factors, including FBP17, Cdc42, and N-WASP...
November 20, 2017: Developmental Cell
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