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Dynamin

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https://www.readbyqxmd.com/read/27903237/leucine-rich-repeat-kinase-2-lrrk2-regulates-%C3%AE-synuclein-clearance-in-microglia
#1
Tatsunori Maekawa, Toshikuni Sasaoka, Sadahiro Azuma, Takafumi Ichikawa, Heather L Melrose, Matthew J Farrer, Fumiya Obata
BACKGROUND: α-Synuclein (αSYN) has been genetically implicated in familial and sporadic Parkinson's disease (PD), and is associated with disease susceptibility, progression and pathology. Excess amounts of αSYN are toxic to neurons. In the brain, microglial αSYN clearance is closely related to neuronal survival. Leucine-rich repeat kinase 2 (LRRK2) is the one of the other genes implicated in familial and sporadic PD. While LRRK2 is known to be expressed in microglia, its true function remains to be elucidated...
November 30, 2016: BMC Neuroscience
https://www.readbyqxmd.com/read/27899210/comparative-analysis-of-the-internalization-of-the-macrophage-receptor-sialoadhesin-in-human-and-mouse-primary-macrophages-and-cell-lines
#2
Marjorie De Schryver, Annelies Leemans, Isabel Pintelon, Davie Cappoen, Louis Maes, Guy Caljon, Paul Cos, Peter L Delputte
Sialoadhesin (Sn) is a surface receptor expressed on resident macrophages with the ability to bind with sialic acids. During inflammation, an upregulation of Sn is observed. Upon binding of monoclonal antibodies to Sn, the receptor becomes internalized and this has been observed in multiple species. The latter characteristic, combined with the strong upregulation of Sn on inflammatory macrophages and the fact that Sn-positive macrophages contribute to certain inflammatory diseases, makes Sn an interesting entry portal for phenotype-modulating or cytotoxic drugs...
November 21, 2016: Immunobiology
https://www.readbyqxmd.com/read/27895162/cannabinoid-receptor-interacting-protein-crip-1a-competition-with-%C3%AE-arrestin-for-cb1-receptor-binding-sites
#3
Lawrence C Blume, Theresa Patten, Khalil Eldeeb, Sandra Leone-Kabler, Alexander A Ilyasov, Bradley M Keegan, Jeremy E O'Neal, Caroline E Bass, Roy R Hantgan, W Todd Lowther, Dana E Selley, Allyn C Howlett
Cannabinoid Receptor Interacting Protein1a (CRIP1a) is a CB1 receptor (CB1R) distal C-terminus-associated protein that alters CB1R interactions with G-proteins (Blume et al.,2015; Smith et al.,2015). We tested the hypothesis that CRIP1a is capable of also altering CB1R interactions with β-arrestin proteins that interact with the CB1R at the C-terminal. Co-immunoprecipitation studies indicated that CB1R associates in complexes with either CRIP1a or β-arrestin, but CRIP1a and β-arrestin fail to co-immunoprecipitate with each other...
November 28, 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27885263/targeting-high-dynamin-2-dnm2-expression-by-restoring-ikaros-function-in-acute-lymphoblastic-leukemia
#4
Zheng Ge, Yan Gu, Qi Han, Gang Zhao, Min Li, Jianyong Li, Baoan Chen, Tianyu Sun, Sinisa Dovat, Robert Peter Gale, Chunhua Song
Dynamin-2 (DNM2) is a GTPase essential for intracellular vesicle formation and trafficking, cytokinesis and receptor endocytosis. Mutations in DNM2 are common in early T-cell precursor acute lymphoblastic leukemia. However, DNM2 expression in other types of ALL are not reported. We studied DNM2 mRNA level in adults with B- and T-cell ALL. We found DNM2 is more highly expressed compared with normals in both forms of ALL. High DNM2 expression is associated with some clinical and laboratory features, inferior outcomes and with leukaemia cell proliferation...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27879341/title-dynamin-functions-and-ligands-classical-mechanism-behind
#5
Mahaveer Singh, Hemant Jadhav, Tanya B
Dynamin is a GTPase, which plays a vital role in clathrin dependent endocytosis and other vesicular trafficking processes. Dynamin acts as scissor with debatable mechanism for newly formed vesicles originating from plasma membrane. Dynamin related proteins are important components in scission of various organelles such as clathrin coated vesicles, phagosomes and mitochondria, etc. helping in organelle division, viral resistance and mitochondrial fusion/division. Dysfunction and mutations in dynamin have been implicated in various disorders, where endocytic trafficking is involved, such as Alzheimer's, Parkinson's, Huntington's, Charcot-Marie Tooth disease, Heart failure, Schizophrenia, Epilepsy, Cancer, Optic atrophy, Down syndrome, Osteoporosis etc...
November 22, 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27875556/mxa-is-a-novel-regulator-of-endosome-associated-transcriptional-signaling-by-bone-morphogenetic-proteins-4-and-9-bmp4-and-bmp9
#6
Huijuan Yuan, Pravin B Sehgal
There is confusion about the role that IFN-α plays in the pathogenesis of pulmonary arterial hypertension (PAH) with different investigators reporting a causative or a protective role. There is now clear evidence in PAH pathogenesis for the involvement of BMP4 and BMP9 signaling, and its disruption by mutations in BMPR2. In the present study, we investigated MxA, an IFN-α-inducible cytoplasmic dynamin-family GTPase for effects on BMP4/9 signaling, including in the presence of PAH-disease-associated mutants of BMPR2...
2016: PloS One
https://www.readbyqxmd.com/read/27872138/micrornas-103-107-coordinately-regulate-macropinocytosis-and-autophagy
#7
Jong Kook Park, Han Peng, Julia Katsnelson, Wending Yang, Nihal Kaplan, Ying Dong, Joshua Z Rappoport, CongCong He, Robert M Lavker
Macropinocytosis, by which cells ingest large amounts of fluid, and autophagy, the lysosome-based catabolic process, involve vesicular biogenesis (early stage) and turnover (end stage). Much is known about early-stage events; however, our understanding of how the end stages of these processes are governed is incomplete. Here we demonstrate that the microRNA-103/107(miR-103/107) family, which is preferentially expressed in the stem cell-enriched limbal epithelium, coordinately regulates aspects of both these activities...
November 21, 2016: Journal of Cell Biology
https://www.readbyqxmd.com/read/27870637/calcium-homeostasis-alterations-in-a-mouse-model-of-the-dynamin-2-related-centronuclear-myopathy
#8
Bodvaël Fraysse, Pascale Guicheney, Marc Bitoun
Autosomal dominant centronuclear myopathy (CNM) is a rare congenital myopathy characterized by centrally located nuclei in muscle fibers. CNM results from mutations in the gene encoding dynamin 2 (DNM2), a large GTPase involved in endocytosis, intracellular membrane trafficking, and cytoskeleton regulation. We developed a knock-in mouse model expressing the most frequent DNM2-CNM mutation; i.e. the KI-Dnm2(R465W) model. Heterozygous (HTZ) KI-Dnm2 mice progressively develop muscle atrophy, impairment of contractile properties, histopathological abnormalities, and elevated cytosolic calcium concentration...
November 15, 2016: Biology Open
https://www.readbyqxmd.com/read/27861739/afzelin-ameliorates-d-galactosamine-and-lipopolysaccharide-induced-fulminant-hepatic-failure-by-modulating-mitochondrial-quality-control-and-dynamics-150-150
#9
Sang-Bin Lee, Jung-Woo Kang, So-Jin Kim, Jongmin Ahn, Jinwoong Kim, Sun-Mee Lee
BACKGROUND AND PURPOSE: Fulminant hepatic failure (FHF) is a fatal clinical syndrome that results in excessive inflammation and hepatocyte death. Mitochondrial dysfunction is considered to be a possible mechanism of FHF. Afzelin, a flavonol glycoside found in Houttuynia cordata Thunberg, has anti-inflammatory and antioxidant properties. The present study elucidated the cytoprotective mechanisms of afzelin against D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced FHF, particularly focusing on mitochondrial quality control and dynamics...
November 15, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27861221/clinical-electrophysiology-and-pathology-features-of-dynamin-centronuclear-myopathy-a-case-report-and-review-of-literature
#10
Sumit Verma, Suman B Balasubramanian
Dynamin (DNM2) centronuclear myopathy (CNM) has variable age of onset, distal greater than proximal muscle weakness, ptosis with or without extraocular muscle weakness, and a characteristic muscle biopsy with radial sarcoplasmic strands giving spoke like appearance. The following case report highlights clinical, electrophysiology, and pathology features of a genetic confirmed DNM2 CNM subject. In addition, a review of literature on all genetic confirmed DNM2 CNM cases published in English literature from 2006 to 2016 is presented...
December 2016: Journal of Clinical Neuromuscular Disease
https://www.readbyqxmd.com/read/27861142/newcastle-disease-virus-employs-macropinocytosis-and-rab5a-dependent-intracellular-trafficking-to-infect-df-1-cells
#11
Lei Tan, Yuqiang Zhang, Yuan Zhan, Yanmei Yuan, Yingjie Sun, Xusheng Qiu, Chunchun Meng, Cuiping Song, Ying Liao, Chan Ding
Oncolytic Newcastle disease virus (NDV) reportedly employs direct fusion of the viral envelope with the plasma membrane and caveolae-dependent endocytosis to enter cells. Here, we show that macropinocytosis and clathrin-mediated endocytosis are involved in NDV entry into a galline embryonic fibroblast cell line. Upon specific inhibition of clathrin assembly, GTPase dynamin, Na+/H+ exchangers, Ras-related C3 botulinum toxin substrate 1, p21 activated kinase 1 or protein kinase C, entry of NDV and its propagation were suppressed...
November 15, 2016: Oncotarget
https://www.readbyqxmd.com/read/27855736/glutamate-is-a-wake-active-neurotransmitter-in-drosophila-melanogaster
#12
John E Zimmerman, May T Chan, Olivia T Lenz, Brendan T Keenan, Greg Maislin, Allan I Pack
STUDY OBJECTIVES: In mammals, there is evidence that glutamate has a role as a wake active neurotransmitter. So using video-based analysis of Drosophila behavior we undertook a study to examine if glutamate, which has been previously shown to have an excitatory role in neuromuscular junctions in Drosophila, may have a conserved wake-active role in the adult brain. METHODS: Using 6-9 day old female flies we examined the effect of perturbations of the glutamatergic signaling on total wakefulness and wake bout architecture...
October 28, 2016: Sleep
https://www.readbyqxmd.com/read/27853797/5-aryl-2-naphtha-1-yl-sulfonamido-thiazol-4-5h-ones-as-clathrin-inhibitors
#13
Mark J Robertson, André Horatscheck, Samantha Sauer, Lisa von Kleist, Jennifer R Baker, Wiebke Stahlschmidt, Marc Nazaré, Ainslie Whiting, Ngoc Chau, Phillip J Robinson, Volker Haucke, Adam McCluskey
The development of a (Z)-5-((6,8-dichloro-4-oxo-4H-chromen-3-yl)methylene)-2-thioxothiazolidin-4-one (2), rhodanine-based lead that led to the Pitstop® 2 family of clathrin inhibitors is described herein. Head group substitution and bioisosteric replacement of the rhodanine core with a 2-aminothiazol-4(5H)-one scaffold eliminated off target dynamin activity. A series of N-substituents gave first phenylglycine (20, IC50 ∼ 20 μM) then phenyl (25, IC50 ∼ 7.1 μM) and 1-napthyl sulfonamide (26, Pitstop® 2 compound, IC50 ∼ 1...
November 17, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27852062/disrupted-in-schizophrenia-1-disc1-inhibits-glioblastoma-development-by-regulating-mitochondria-dynamics
#14
Xingchun Gao, Yajing Mi, Na Guo, Zhifang Hu, Fengrui Hu, Dou Liu, Lei Gao, Xingchun Gou, Weilin Jin
Glioblastoma(GBM) is one of the most common and aggressive malignant primary tumors of the central nervous system and mitochondria have been proposed to participate in GBM tumorigenesis. Previous studies have identified a potential role of Disrupted in Schizophrenia 1 (DISC1), a multi-compartmentalized protein, in mitochondria. But whether DISC1 could regulate GBM tumorigenesis via mitochondria is still unknown. We determined the expression level of DISC1 by both bioinformatics analysis and tissue analysis, and found that DISC1 was highly expressed in GBM...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27844171/mitochondrial-dynamics-as-a-therapeutic-target-for-treating-cardiac-diseases
#15
Sang-Bing Ong, Derek J Hausenloy
Mitochondria are dynamic in nature and are able to shift their morphology between elongated interconnected mitochondrial networks and a fragmented disconnected arrangement by the processes of mitochondrial fusion and fission, respectively. Changes in mitochondrial morphology are regulated by the mitochondrial fusion proteins - mitofusins 1 and 2 (Mfn1 and 2), and optic atrophy 1 (Opa1) as well as the mitochondrial fission proteins - dynamin-related peptide 1 (Drp1) and fission protein 1 (Fis1). Despite having a unique spatial arrangement, cardiac mitochondria have been implicated in a variety of disorders including ischemia-reperfusion injury (IRI), heart failure, diabetes, and pulmonary hypertension...
November 15, 2016: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/27837024/chloroplast-division-checkpoint-in-eukaryotic-algae
#16
Nobuko Sumiya, Takayuki Fujiwara, Atsuko Era, Shin-Ya Miyagishima
Chloroplasts evolved from a cyanobacterial endosymbiont. It is believed that the synchronization of endosymbiotic and host cell division, as is commonly seen in existing algae, was a critical step in establishing the permanent organelle. Algal cells typically contain one or only a small number of chloroplasts that divide once per host cell cycle. This division is based partly on the S-phase-specific expression of nucleus-encoded proteins that constitute the chloroplast-division machinery. In this study, using the red alga Cyanidioschyzon merolae, we show that cell-cycle progression is arrested at the prophase when chloroplast division is blocked before the formation of the chloroplast-division machinery by the overexpression of Filamenting temperature-sensitive (Fts) Z2-1 (Fts72-1), but the cell cycle progresses when chloroplast division is blocked during division-site constriction by the overexpression of either FtsZ2-1 or a dominant-negative form of dynamin-related protein 5B (DRP5B)...
November 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27831567/erk-drp1-dependent-mitochondrial-fission-is-involved-in-the-msc-induced-drug-resistance-of-t-cell-acute-lymphoblastic-leukemia-cells
#17
Jianye Cai, Jiancheng Wang, Yinong Huang, Haoxiang Wu, Ting Xia, Jiaqi Xiao, Xiaoyong Chen, Hongyu Li, Yuan Qiu, Yingnan Wang, Tao Wang, Huimin Xia, Qi Zhang, Andy Peng Xiang
The bone marrow microenvironment facilitates the proliferation and survival of leukemia cells, contributing to disease relapse. Bone marrow-derived mesenchymal stem cells (MSCs) are well known to promote cancer chemoresistance via soluble factors and cell adhesion. However, little is known about the effects of MSCs on the mitochondrial dynamics of T-cell acute lymphoblastic leukemia (T-ALL) cells, or how this may influence the chemoresistance of these cells. Here, we tested both indirect (Transwell) and direct coculture strategies, and found that MSCs protected T-ALL cells from chemotherapeutic cell death and cytotoxicity under both culture conditions...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27830583/dynamin-related-protein-1-drp1-mediating-mitophagy-contributes-to-the-pathophysiology-of-nervous-system-diseases-and-brain-injury
#18
REVIEW
Qiong Wu, Cheng-Liang Luo, Lu-Yang Tao
As the main source of energy (celluar ATP) in eukaryotic cells, mitochondria are involved in cellular physiology and pathology. The balance of mitochondrial dynamic, fission and fusion regulated by quality control mechanisms, provides a guarantee for maintaining mitochondrial function, even celluar function. Worn out mitochondria would be removed through mitophagy which is regulated by autophagy related proteins and mitochondrial membrane proteins. Drp1, dynamic-related protein 1, is regarded as one of the most important proteins to evaluate mitochondrial fission mediating mitophagy in neurodegenerative diseases (eg...
November 10, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/27824116/ddr1-promotes-e-cadherin-stability-via-inhibition-of-integrin-%C3%AE-1-src-activation-mediated-e-cadherin-endocytosis
#19
Hong-Ru Chen, Yi-Chun Yeh, Ching-Yi Liu, Yu-Ting Wu, Fang-Yu Lo, Ming-Jer Tang, Yang-Kao Wang
Discoidin domain receptor 1 (DDR1), a receptor tyrosine kinase of collagen, is primarily expressed in epithelial cells. Activation of DDR1 stabilises E-cadherin located on the cell membrane; however, the detailed mechanism of DDR1-stabilised E-cadherin remains unclear. We performed DDR1 knockdown (Sh-DDR1) on Mardin-Darby canine kidney cells to investigate the mechanism of DDR1-stabilised E-cadherin. Sh-DDR1 decreased junctional localisation, increased endocytosis of E-cadherin, and increased physical interactions between E-cadherin and clathrin...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27822712/dynasore-improves-motor-function-recovery-via-inhibition-of-neuronal-apoptosis-and-astrocytic-proliferation-after-spinal-cord-injury-in-rats
#20
Gang Li, Feifei Shen, Zhongkai Fan, Yangsong Wang, Xiangquan Kong, Deshui Yu, Xiaodong Zhi, Gang Lv, Yang Cao
Spinal cord injury (SCI) is a common and devastating central nervous system insult which lacks efficient treatment. Our previous experimental findings indicated that dynamin-related protein 1 (Drp1) mediates mitochondrial fission during SCI, and inhibition of Drp1 plays a significant protective effect after SCI in rats. Dynasore inhibits GTPase activity at both the plasma membrane (dynamin 1, 2) and the mitochondria membrane (Drp1). The aim of the present study was to investigate the beneficial effects of dynasore on SCI and its underlying mechanism in a rat model...
November 7, 2016: Molecular Neurobiology
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