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https://www.readbyqxmd.com/read/28067790/rab10-interacts-with-the-male-germ-cell-specific-gtpase-activating-protein-during-mammalian-spermiogenesis
#1
Ying-Hung Lin, Chih-Chun Ke, Ya-Yun Wang, Mei-Feng Chen, Tsung-Ming Chen, Wei-Chi Ku, Han-Sun Chiang, Chung-Hsin Yeh
According to recent estimates, 2%-15% of couples are sterile, and approximately half of the infertility cases are attributed to male reproductive factors. However, the reasons remain undefined in approximately 25% of male infertility cases, and most infertility cases exhibit spermatogenic defects. Numerous genes involved in spermatogenesis still remain unknown. We previously identified Male Germ Cells Rab GTPase-Activating Proteins (MGCRABGAPs) through cDNA microarray analysis of human testicular tissues with spermatogenic defects...
January 5, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28063499/analysis-of-phosphatidic-acid-binding-and-regulation-of-pipki-in-vitro-and-in-intact-cells
#2
L W R Tay, Z Wang, G Du
Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a lipid second messenger that regulates a wide array of essential cellular events, such as signal transduction, vesicle trafficking, actin cytoskeleton dynamics, adhesion, and motility. To control the spatiotemporal production of PI(4,5)P2, the activity of type 1 phosphotidylinositol-4-phosphate-5-kinases (PIPKIs) is tightly regulated by small GTPases and another signaling lipid, phosphatidic acid (PA). It is of interest that PI(4,5)P2 is also a critical cofactor for the activation of the PA-generating enzyme, phospholipase D (PLD)...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28062848/the-spectraplakin-short-stop-is-an-essential-microtubule-regulator-involved-in-epithelial-closure-in-drosophila
#3
Zsanett Takács, Ferenc Jankovics, Péter Vilmos, Péter Lénárt, Katja Röper, Miklós Erdélyi
Dorsal closure of the Drosophila embryonic epithelium provides an excellent model system for the in vivo analysis of molecular mechanisms regulating cytoskeletal rearrangements. We investigated the function of the Drosophila spectraplakin Short stop (Shot), a conserved cytoskeletal structural protein, during closure of the dorsal embryonic epithelium.In this study, we show that Shot is essential for the efficient final zippering of the opposing epithelial margins. Using isoform-specific mutant alleles and genetic rescue experiments with truncated Shot variants, we demonstrate that Shot functions as an actin-microtubule cross-linker in mediating zippering...
January 6, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28062165/daboialectin-a-c-type-lectin-from-russell-s-viper-venom-induces-cytoskeletal-damage-and-apoptosis-in-human-lung-cancer-cells-in%C3%A2-vitro
#4
Jigni Pathan, Sukanta Mondal, Angshuman Sarkar, Dibakar Chakrabarty
'Daboialectin', a low molecular weight C-type lectin (18.5 kDa) isolated from Russell's viper venom showed cytotoxic effects on human broncho-alveolar carcinoma derived (A549) cell lines. Daboialectin induced inhibition of A549 cell growth was time and concentration dependent with severe morphological changes by altering the functions of small GTPases such as Rac, Rho and cdc42. ROS induced DNA damage may result in apoptosis by inducing disruption of membrane integrity, blebbing and nuclear disintegration by activating caspases...
January 3, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28060719/temporal-quantitative-phosphoproteomics-of-adp-stimulation-reveals-novel-central-nodes-in-platelet-activation-and-inhibition
#5
Florian Beck, Jörg Geiger, Stepan Gambaryan, Fiorella A Solari, Margherita Dell'Aica, Stefan Loroch, Nadine Mattheij, Igor Mindukshev, Oliver Pötz, Kerstin Jurk, Julia M Burkhart, Christian Fufezan, Johan W M Heemskerk, Ulrich Walter, René P Zahedi, Albert Sickmann
ADP enhances platelet activation by virtually any other stimulant to complete aggregation. It binds specifically to the G-protein coupled membrane receptors P2Y1 and P2Y12, stimulating intracellular signaling cascades leading to integrin αIIbβ3 activation, a process that is antagonized by endothelial prostacyclin. P2Y12 inhibitors are among the most successful anti-platelet drugs, however, show remarkable variability in efficacy. We reasoned whether a more detailed molecular understanding of ADP-induced protein phosphorylation could identify (i) critical hubs in platelet signaling towards aggregation, and (ii) novel molecular targets for anti-platelet treatment strategies...
November 9, 2016: Blood
https://www.readbyqxmd.com/read/28051168/mechanisms-of-yersinia-yopo-kinase-substrate-specificity
#6
Wei Lin Lee, Pavithra Singaravelu, Sheena Wee, Bo Xue, Khay Chun Ang, Jayantha Gunaratne, Jonathan M Grimes, Kunchithapadam Swaminathan, Robert C Robinson
Yersinia bacteria cause a range of human diseases, including yersiniosis, Far East scarlet-like fever and the plague. Yersiniae modulate and evade host immune defences through injection of Yersinia outer proteins (Yops) into phagocytic cells. One of the Yops, YopO (also known as YpkA) obstructs phagocytosis through disrupting actin filament regulation processes - inhibiting polymerization-promoting signaling through sequestration of Rac/Rho family GTPases and by using monomeric actin as bait to recruit and phosphorylate host actin-regulating proteins...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28043012/tnf-alpha-stimulation-increases-dental-pulp-stem-cell-migration-in-vitro-through-integrin-alpha-6-subunit-upregulation
#7
Lei Shi, Shanqi Fu, Sidra Fahim, Shuang Pan, He Lina, Xiaodan Mu, Yumei Niu
OBJECTIVE: The dissemination of stem cells into tissues requiring inflammatory and reparative response is fundamentally dependent upon their chemotactic migration. Expression of TNF-α is up regulated in inflamed pulps. Dental pulp cells are also known to express integrin α6 subunit. Expression of integrin subunit α6 has been linked to the acquisition of migratory potential in a wide variety of cell types in both pathological and physiological capacities. Therefore, in this study we examined the effects of a pleiotropic cytokine TNF-α on the migration of hDPSCs and investigated its relationship with expression of integrin α6 in hDPSCs during chemotactic migration...
December 15, 2016: Archives of Oral Biology
https://www.readbyqxmd.com/read/28042766/insights-into-the-regulation-of-yap-taz-from-cellular-systems-and-mouse-models
#8
Wei Du, Wen Du, Mian Wan, Xuedong Zhou, Xin Xu, Liwei Zheng
The Hippo signaling pathway serves as a main regulator of tissue growth and organ size through the moderation of cell cycle dynamics across many different species. In mammals, the two downstream transcriptional regulators of this pathway are Yes-associated protein (YAP) and transcriptional co-activator with PDZ binding motif (TAZ). Recent studies found in addition to the core Hippo signaling pathway, other signaling pathways can also regulate YAP/TAZ activity, either directly or through crosstalk with the Hippo pathway...
January 2, 2017: Current Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28039206/endoplasmic-reticulum-chaperone-gp96-controls-actomyosin-dynamics-and-protects-against-pore-forming-toxins
#9
Francisco Sarmento Mesquita, Cláudia Brito, Maria J Mazon Moya, Jorge Campos Pinheiro, Serge Mostowy, Didier Cabanes, Sandra Sousa
During infection, plasma membrane (PM) blebs protect host cells against bacterial pore-forming toxins (PFTs), but were also proposed to promote pathogen dissemination. However, the details and impact of blebbing regulation during infection remained unclear. Here, we identify the endoplasmic reticulum chaperone Gp96 as a novel regulator of PFT-induced blebbing. Gp96 interacts with non-muscle myosin heavy chain IIA (NMHCIIA) and controls its activity and remodelling, which is required for appropriate coordination of bleb formation and retraction...
December 30, 2016: EMBO Reports
https://www.readbyqxmd.com/read/28035049/opposing-roles-for-distinct-linc-complexes-in-regulation-of-the-small-gtpase-rhoa
#10
Ketan Thakar, Christopher K May, Anna Rogers, Christopher W Carroll
Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes span the nuclear envelope and transduce force from dynamic cytoskeletal networks to the nuclear lamina. Here we show that LINC complexes also signal from the nuclear envelope to critical regulators of the actin cytoskeleton. Specifically, we find that LINC complexes that contain the inner nuclear membrane protein Sun2 promote focal adhesion assembly by activating the small GTPase RhoA. A key effector in this process is the transcription factor/coactivator complex composed of SRF/Mkl1...
January 1, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28032931/fkbp51-regulates-cell-motility-and-invasion-via-rhoa-signaling
#11
Miho Takaoka, Shun Ito, Yoshio Miki, Akira Nakanishi
FK506 binding protein 51 (FKBP51), a member of the immunophilin family, is involved in multiple signaling pathways, tumorigenesis, and chemoresistance. FKBP51 expression correlates with metastatic potential in melanoma and prostate cancer. However, the functions of FKBP51, particularly involving the regulation of cell motility and invasion, are not fully understood. We discovered two novel interacting partner proteins of FKBP51, i.e., deleted in liver cancer 1 (DLC1) and deleted in liver cancer 2 (DLC2), using immunoprecipitation and mass spectrometry...
December 29, 2016: Cancer Science
https://www.readbyqxmd.com/read/28028053/mrtf-potentiates-tead-yap-transcriptional-activity-causing-metastasis
#12
Tackhoon Kim, Daehee Hwang, Dahye Lee, Jeong-Hwan Kim, Seon-Young Kim, Dae-Sik Lim
Yes-associated protein (YAP) and myocardin-related transcription factor (MRTF) play similar roles and exhibit significant crosstalk in directing transcriptional responses to chemical and physical extracellular cues. The mechanism underlying this crosstalk, however, remains unclear. Here, we show MRTF family proteins bind YAP via a conserved PPXY motif that interacts with the YAP WW domain. This interaction allows MRTF to recruit NcoA3 to the TEAD-YAP transcriptional complex and potentiate its transcriptional activity...
December 27, 2016: EMBO Journal
https://www.readbyqxmd.com/read/28025149/substrate-stiffness-promotes-latent-tgf-%C3%AE-1-activation-in-hepatocellular-carcinoma
#13
Mingshu Pang, Yao Teng, Jianyong Huang, Yuan Yuan, Feng Lin, Chunyang Xiong
Hepatocellular carcinoma (HCC) was usually coupled with increased stiffness of the extracellular matrix (ECM) and elevated level of transforming growth factor-β1 (TGF-β1). However, the mechanism by which substrate rigidity modulated TGF-β1 signaling transduction remained unknown. This paper investigated the molecular mechanism of how matrix stiffness regulating TGF-β1 signaling in HCC cells. By means of stiffness tunable collagen I-coated polyacrylamide (PA) gels, we found that the expressions of β1 integrin, p-FAK (Y397) and p-Smad2 upregulated on stiffer gels as well as the content of TGF-β1 in culture media of HCC cells, which were inhibited by RGD blocking peptides, Y-27632 (ROCK inhibitor) or Blebbistatin (myosin II inhibitor)...
December 24, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28019696/crmp4-inhibits-bone-formation-by-negatively-regulating-bmp-and-rhoa-signaling
#14
Basem M Abdallah, Florence Figeac, Kenneth H Larsen, Nicholas Ditzel, Pankaj Keshari, Adiba Isa, Abbas Jafari, Thomas L Andersen, Jean-Marie Delaisse, Yoshio Goshima, Toshio Ohshima, Moustapha Kassem
We identified the neuro-protein CRMP4 (collapsing response mediator protein-4) as a non-canonical osteogenic factor that regulating the differentiation of mouse bone marrow skeletal stem cells (bone marrow stromal stem cells, mBMSCs) into osteoblastic cells. CRMP4 is the only member of the CRMP 1-5 family to be expressed by mBMSCs and in osteoprogenitors of both adult mouse and human bones. In vitro gain and loss function of CRMP4 in murine stromal cells revealed its inhibitory effect on osteoblast differentiation...
December 26, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28003226/canstatin-stimulates-migration-of-rat-cardiac-fibroblasts-via-secretion-of-matrix-metalloproteinase-2
#15
Muneyoshi Okada, Naoki Murata, Hideyuki Yamawaki
Type IV collagen, a non-fibrillar type, is ubiquitously expressed in the basement membrane around cardiomyocytes. Canstatin, a cleaved product of α2 chain of type IV collagen, is an anti-angiogenic factor. Because it has not been clarified whether canstatin exerts other biological activities in heart, we investigated the effects of canstatin on adult rat cardiac fibroblasts. Cell migration was determined by Boyden chamber assay. Western blotting was performed to detect secretion of matrix metalloproteinase (MMP)-2 and MMP-9 and phosphorylation of extracellular signal-regulated kinase (ERK)...
December 21, 2016: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/27998979/alpha-actinin-4-actn4-regulates-glucocorticoid-receptor-mediated-transactivation-and-transrepression-in-podocytes
#16
Xuan Zhao, Simran Khurana, Sharmistha Charkraborty, Yuqian Tian, John R Sedor, Leslie A Bruggeman, Hung-Ying Kao
Glucocorticoids (GCs) are a general class of steroids that possess renoprotective activity in glomeruli through their interaction with the glucocorticoid receptor. However, the mechanisms by which the GCs ameliorate proteinuria and glomerular disease are not well understood. In this study, we demonstrated that alpha actinin 4 (ACTN4), an actin-crosslinking protein known to coordinate cytoskeletal organization, interacts with the glucocorticoid receptor (GR) in the nucleus of human podocytes (HPCs), a key cell type in the glomerulus critical for kidney filtration function...
December 20, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27997810/glut-1-dependent-glycolysis-is-increased-during-aging-related-lung-fibrosis-and-phloretin-inhibits-lung-fibrosis
#17
Soo Jung Cho, Jong-Seok Moon, Chang-Min Lee, Augustine M K Choi, Heather W Stout-Delgado
RATIONAL: Aging is associated with metabolic diseases such as type 2 diabetes mellitus, cardiovascular disease, cancer and neurodegeneration. Aging contributes to common processes including metabolic dysfunction, DNA damage and reactive oxygen species generation. While glycolysis has been linked to cell growth and proliferation, the mechanisms by which the activation of glycolysis by aging regulates fibrogenesis in lung remain unclear. OBJECTIVES: To determine if glucose transport 1 (GLUT1)-induced glycolysis regulates age-dependent fibrogenesis of the lung...
December 20, 2016: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27995769/triad3-rnf216-mutations-associated-with-gordon-holmes-syndrome-lead-to-synaptic-and-cognitive-impairments-via-arc-misregulation
#18
Nilofer Husain, Qiang Yuan, Yi-Chun Yen, Olga Pletnikova, Dong Qianying Sally, Paul Worley, Zoë Bichler, H Shawn Je
Multiple loss-of-function mutations in TRIAD3 (a.k.a. RNF216) have recently been identified in patients suffering from Gordon Holmes syndrome (GHS), characterized by cognitive decline, dementia, and movement disorders. TRIAD3A is an E3 ubiquitin ligase that recognizes and facilitates the ubiquitination of its target for degradation by the ubiquitin-proteasome system (UPS). Here, we demonstrate that two of these missense substitutions in TRIAD3 (R660C and R694C) could not regulate the degradation of their neuronal target, activity-regulated cytoskeletal-associated protein (Arc/Arg 3...
December 20, 2016: Aging Cell
https://www.readbyqxmd.com/read/27995685/taadf4-an-actin-depolymerizing-factor-from-wheat-is-required-for-resistance-to-the-stripe-rust-pathogen-puccinia-striiformis-f-sp-tritici
#19
Bing Zhang, Yuan Hua, Juan Wang, Yan Huo, Masaki Shimono, Brad Day, Qing Ma
Actin filament assembly in plants is a dynamic process, requiring the activity of more than 75 actin-binding proteins. Central to the regulation of filament assembly and stability is the activity of a conserved family of actin-depolymerizing factors (ADFs), whose primarily function is to regulate actin filament severing and depolymerization. In recent years, the activity of ADF proteins has been linked to a variety of cellular processes, including those associated with response to stress. Herein, a wheat ADF gene, TaADF4, was identified and characterized...
December 20, 2016: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/27993196/milk-fat-globule-epidermal-growth-factor-factor-viii-derived-peptide-msp68-is-a-cytoskeletal-immunomodulator-of-neutrophils-that-inhibits-rac1
#20
Louie Hendricks, Monowar Aziz, Weng-Lang Yang, Jeffrey Nicastro, Gene F Coppa, Marc Symons, Ping Wang
BACKGROUND: Prolonged neutrophil infiltration leads to exaggerated inflammation and tissue damage during sepsis. Neutrophil migration requires rearrangement of their cytoskeleton. Milk fat globule-epidermal growth factor-factor VIII-derived short peptide 68 (MSP68) has recently been shown to be beneficial in sepsis-induced tissue injury and mortality. We hypothesize that MSP68 inhibits neutrophil migration by modulating small GTPase Rac1-dependent cytoskeletal rearrangements. METHODS: Bone marrow-derived neutrophils (BMDNs) or whole lung digest isolated neutrophils were isolated from 8 to 10 wk old C57BL/6 mice by Percoll density gradient centrifugation...
February 2017: Journal of Surgical Research
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