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Non muscle myosin IIA

Yijie Chen, Yang Yu, Shuya Sun, Zhaotong Wang, Peiqing Liu, Shenglan Liu, Jianmin Jiang
Tumor metastasis is the main reason of death for hepatocellular carcinoma (HCC) patients. Cell migration and invasion are two prerequisites for tumor metastasis, in which TRPM7 and MMPs play an important role. In our study, we found that bradykinin (BK) could upregulate the expression of TRPM7 and dynamically regulate the phosphorylation of non-muscle myosin IIA heavy chain (NMHC-IIA) Ser-1943 in HepG2 cells. The influx of Ca(2+) via TRPM7 was necessary for elevating the activity of m-calpain and μ-calpain...
September 30, 2016: Experimental Cell Research
Andrew C Fry, Terry J Housh, Joel B Cramer, Joseph P Weir, Travis W Beck, Brian K Schilling, Jonathan D Miller, Justin X Nicoll
Numerous conditions and types of physical activity (e.g., exercise, aging, muscle-related diseases) can influence muscle fiber types and the proteins expressed. To date, muscle fibers can only be characterized by actually obtaining a tissue sample using the invasive muscle biopsy procedure. Mechanomyography (MMG) is the assessment of the vibration properties of contracting skeletal muscle, and has been proposed as a possible non-invasive method for muscle fiber analysis. Therefore, the purpose of this project was to examine the feasibility of using MMG and muscle performance measures to non-invasively assess muscle fiber characteristics...
September 20, 2016: Journal of Strength and Conditioning Research
Zhipeng Xu, Peng Li, Dan Wei, Zhixiang Wang, Yi Bao, Jipeng Sun, Le Qu, Linhui Wang
The chemokine receptor cysteine (C)-X-C receptor (CXCR4) is a G-protein-coupled receptor that exerts a vital role in distant metastasis of renal cell carcinoma (RCC). Emerging evidence demonstrates that CXCR4 as the cytomembrane receptor translocated into the nucleus to facilitate cell migration and, therefore, determine the prognosis of several types of malignancies. However, the biological mechanism of nuclear location of CXCR4 remains unclear. In the present study, we confirmed the significant implications of the putative nuclear localization sequence (NLS) '146RPRK149̓ on CXCR4 subcellular localization and metastatic potential by point-mutation assay in RCC cell lines...
September 12, 2016: Oncology Reports
Armen Petrosyan, Carol A Casey, Pi-Wan Cheng
Abnormalities in the Golgi apparatus function are important to the development of alcoholic liver injury. We recently reported that Golgi disorganization in ethanol (EtOH)-treated hepatocytes is caused by impaired dimerization of the largest Golgi matrix protein, giantin. However, little is known about the mechanism which forces fragmentation. Here, in both HepG2 cells overexpressing alcohol dehydrogenase and in rat hepatocytes, we found that EtOH administration reduces the complex between giantin and Rab6a GTPase and results in the S1943 phosphorylation of non-muscle Myosin IIA (NMIIA) heavy chain, thus facilitating NMIIA association with Golgi enzymes, as detected by biochemical approaches and 3D Structured Illumination Microscopy...
2016: Scientific Reports
Tsugumichi Saito, Shuichi Okada, Yoko Shimoda, Yuko Tagaya, Aya Osaki, Eijiro Yamada, Ryo Shibusawa, Yasuyo Nakajima, Atsushi Ozawa, Tetsurou Satoh, Masatomo Mori, Masanobu Yamada
Expression of adaptor protein, phosphotyrosine interaction, pleckstrin homology domain, and leucine zipper containing 1 (APPL1) promoted glucose transporter 4 (GLUT4) translocation and glucose uptake in adipose and muscle tissues in response to stimulation with insulin, adiponectin, or exercise. In response to mechanical stretch, knockdown of APPL1 in C2C12 myotubes suppressed glucose uptake. APPL1-induced increased glucose uptake was mediated by protein kinase C (PKC) ζ but not AKT, AMPK, or calmodulin-dependent protein kinase...
November 2016: Cellular Signalling
Gyula Pálfy, Bence Kiss, László Nyitray, Andrea Bodor
Dysregulation in Ca2+-binding S100 proteins playsimportant role in various diseases. The asymmetric complex of Ca2+-loaded S100A4 with non-muscle myosin IIA has highstability and highly increased Ca2+-affinity. Here weinvestigated the possible causes of this allosteric effect by NMR spectroscopic approaches. Chemical shift basedsecondary structure analysis did not show substantial changes for the complex. Backbone dynamics revealed slow time-scale local motions in the H1 helices of the homodimeric S100A4,which diminished in the complex and could be accompanied by an increase in dimer stability...
July 15, 2016: Chembiochem: a European Journal of Chemical Biology
Huy Quang Le, Sushmita Ghatak, Ching-Yan Chloé Yeung, Frederik Tellkamp, Christian Günschmann, Christoph Dieterich, Assa Yeroslaviz, Bianca Habermann, Ana Pombo, Carien M Niessen, Sara A Wickström
Tissue mechanics drive morphogenesis, but how forces are sensed and transmitted to control stem cell fate and self-organization remains unclear. We show that a mechanosensory complex of emerin (Emd), non-muscle myosin IIA (NMIIA) and actin controls gene silencing and chromatin compaction, thereby regulating lineage commitment. Force-driven enrichment of Emd at the outer nuclear membrane of epidermal stem cells leads to defective heterochromatin anchoring to the nuclear lamina and a switch from H3K9me2,3 to H3K27me3 occupancy at constitutive heterochromatin...
August 2016: Nature Cell Biology
Sang-Joo Kim, Seokwon Lee, Hong-Joon Park, Tae-Hun Kang, Borum Sagong, Jeong-In Baek, Se-Kyung Oh, Jae Young Choi, Kyu-Yup Lee, Un-Kyung Kim
BACKGROUND: Myosin is a key protein involved in regulating the shape and motility of cells. The MYH9 and MYH14 genes, which encode non-muscle myosin heavy chain IIA (NMMHC II-A) and IIC (NMMHC II-C), respectively, are expressed in the inner ear. These myosin genes are known to be associated with autosomal dominant non-syndromic hearing loss (ADNSHL); however, genetic studies in patients with ADNSHL in Korea have rarely been reported. METHODS: We analyzed the MYH9 and MYH14 genes in 75 Korean patients with ADNSHL...
October 10, 2016: Gene
Xiao-Hui Wei, Sen-Sen Lin, Yang Liu, Ren-Ping Zhao, Ghulam Jilany Khan, Hong-Zhi Du, Ting-Ting Mao, Bo-Yang Yu, Rui-Ming Li, Sheng-Tao Yuan, Li Sun
Cancer metastasis plays a major role in tumor deterioration. Metastatic processes are known to be regulated by hypoxic microenvironment and non-muscle myosin IIA (NMIIA). DT-13, a bioactive saponin monomer isolated from Ophiopogon japonicus, has been reported to inhibit various cancer metastasis, but whether NMIIA is involved in the anti-metastatic activity of DT-13 under hypoxia remains to be determined. Thus, this study aims to clarify the role of DT-13 in regulating 95D cell metastasis under hypoxic microenvironment and to further investigate whether NMIIA is involved in the anti-metastatic mechanism of DT-13...
August 2016: Oncology Reports
Hongzhi Du, Yue Huang, Xiaoyin Hou, Xiaowen Yu, Sensen Lin, Xiaohui Wei, Ruiming Li, Ghulam Jilany Khan, Shengtao Yuan, Li Sun
Tumor metastasis is one of the main causes of mortality among patients with malignant tumors. Previous studies concerning tumor metastasis have merely focused on the cancer cells in the tumor. However, an increasing number of studies show that the tumor microenvironment plays a vital role in the progression of cancer, particularly in tumor metastasis. Since fibroblasts and adipocytes are two of the most representative mesenchymal cells in the tumor microenvironment, we established a hypoxia-induced cancer-associated fibroblast (CAF) model and a chemically induced adipocyte model to reveal the effect of the microenvironment on cancer development...
August 2016: Oncology Reports
Tongchao Li, Nikolaos Giagtzoglou, Daniel F Eberl, Sonal Nagarkar Jaiswal, Tiantian Cai, Dorothea Godt, Andrew K Groves, Hugo J Bellen
Myosins play essential roles in the development and function of auditory organs and multiple myosin genes are associated with hereditary forms of deafness. Using a forward genetic screen in Drosophila, we identified an E3 ligase, Ubr3, as an essential gene for auditory organ development. Ubr3 negatively regulates the mono-ubiquitination of non-muscle Myosin II, a protein associated with hearing loss in humans. The mono-ubiquitination of Myosin II promotes its physical interaction with Myosin VIIa, a protein responsible for Usher syndrome type IB...
2016: ELife
Philip A Bondzie, Hui A Chen, Mei Zhen Cao, Julie A Tomolonis, Fangfang He, Martin R Pollak, Joel M Henderson
Several glomerular pathologies resulting from podocyte injury are linked to genetic variation involving the MYH9 gene, which encodes the heavy chain of non-muscle myosin-IIA (NM-IIA). However, the functional role of NM-IIA has not been studied extensively in podocytes. We hypothesized that NM-IIA is critical for maintenance of podocyte structure and mechanical function. To test this hypothesis, we studied murine podocytes in vitro subjected to blebbistatin inhibition of NM-II activity, or RNA interference-mediated, isoform-specific ablation of Myh9 gene and protein (NM-IIA) or its paralog Myh10 gene and protein (NM-IIB)...
August 2016: Cytoskeleton
Joshua E Mangum, Justin P Hardee, Dennis K Fix, Melissa J Puppa, Johnathon Elkes, Diego Altomare, Yelena Bykhovskaya, Dean R Campagna, Paul J Schmidt, Anoop K Sendamarai, Hart G W Lidov, Shayne C Barlow, Nathan Fischel-Ghodsian, Mark D Fleming, James A Carson, Jeffrey R Patton
Mitochondrial myopathy with lactic acidosis and sideroblastic anemia (MLASA) is an oxidative phosphorylation disorder, with primary clinical manifestations of myopathic exercise intolerance and a macrocytic sideroblastic anemia. One cause of MLASA is recessive mutations in PUS1, which encodes pseudouridine (Ψ) synthase 1 (Pus1p). Here we describe a mouse model of MLASA due to mutations in PUS1. As expected, certain Ψ modifications were missing in cytoplasmic and mitochondrial tRNAs from Pus1(-/-) animals...
2016: Scientific Reports
Eric S Schiffhauer, Tianzhi Luo, Krithika Mohan, Vasudha Srivastava, Xuyu Qian, Eric R Griffis, Pablo A Iglesias, Douglas N Robinson
To change shape, divide, form junctions, and migrate, cells reorganize their cytoskeletons in response to changing mechanical environments [1-4]. Actin cytoskeletal elements, including myosin II motors and actin crosslinkers, structurally remodel and activate signaling pathways in response to imposed stresses [5-9]. Recent studies demonstrate the importance of force-dependent structural rearrangement of α-catenin in adherens junctions [10] and vinculin's molecular clutch mechanism in focal adhesions [11]...
June 6, 2016: Current Biology: CB
Jihwa Chung, Hyunbo Shim, Kwanchang Kim, Duhwan Lee, Won Jong Kim, Dong Hoon Kang, Sang Won Kang, Hanjoong Jo, Kihwan Kwon
Atherosclerosis occurs preferentially in arterial regions exposed to disturbed blood flow. Targeting these pro-atherogenic regions is a potential anti-atherogenic therapeutic approach, but it has been extremely challenging. Here, using in vivo phage display approach and the partial carotid ligation model of flow-induced atherosclerosis in mouse, we identified novel peptides that specifically bind to endothelial cells (ECs) exposed to disturbed flow condition in pro-atherogenic regions. Two peptides, CLIRRTSIC and CPRRSHPIC, selectively bound to arterial ECs exposed to disturbed flow not only in the partially ligated carotids but also in the lesser curvature and branching point of the aortic arch in mice as well as human pulmonary artery branches...
2016: Scientific Reports
Antonina J Kruppa, John Kendrick-Jones, Folma Buss
Myosin motor proteins working together with the actin cytoskeleton drive a wide range of cellular processes. In this review, we focus on their roles in autophagy - the pathway the cell uses to ensure homeostasis by targeting pathogens, misfolded proteins and damaged organelles for degradation. The actin cytoskeleton regulated by a host of nucleating, anchoring and stabilizing proteins provides the filament network for the delivery of essential membrane vesicles from different cellular compartments to the autophagosome...
August 2016: Traffic
Konstantin Popov, James Komianos, Garegin A Papoian
Active matter systems, and in particular the cell cytoskeleton, exhibit complex mechanochemical dynamics that are still not well understood. While prior computational models of cytoskeletal dynamics have lead to many conceptual insights, an important niche still needs to be filled with a high-resolution structural modeling framework, which includes a minimally-complete set of cytoskeletal chemistries, stochastically treats reaction and diffusion processes in three spatial dimensions, accurately and efficiently describes mechanical deformations of the filamentous network under stresses generated by molecular motors, and deeply couples mechanics and chemistry at high spatial resolution...
April 2016: PLoS Computational Biology
Joanna Zaleska, Katarzyna Skorka, Malgorzata Zajac, Agnieszka Karczmarczyk, Marta Karp, Waldemar Tomczak, Marek Hus, Paulina Wlasiuk, Krzysztof Giannopoulos
Mounting evidence suggests that autoreactivity and inflammatory processes are involved in the pathogenesis of chronic lymphocytic leukaemia (CLL). Cytoskeletal proteins, including non-muscle myosin heavy chain IIA (MYHIIA), vimentin (VIM) and cofilin-1 (CFL1), exposed on the surface of apoptotic cells have been identified as autoantigens that are recognized by the specific B-cell receptors of the CLL cells. In 212 CLL patients analysed with quantitative reverse transcriptase-polymerase chain reaction we found CFL1 overexpression and low expression of MYH9 in comparison with healthy volunteers...
August 2016: British Journal of Haematology
Nayden G Naydenov, Alex Feygin, Dongdong Wang, John F Kuemmerle, Gianni Harris, Mary Anne Conti, Robert S Adelstein, Andrei I Ivanov
The actin cytoskeleton is a critical regulator of intestinal mucosal barrier permeability, and the integrity of epithelial adherens junctions (AJ) and tight junctions (TJ). Non muscle myosin II (NM II) is a key cytoskeletal motor that controls actin filament architecture and dynamics. While NM II has been implicated in the regulation of epithelial junctions in vitro, little is known about its roles in the intestinal mucosa in vivo. In this study, we generated a mouse model with an intestinal epithelial-specific knockout of NM IIA heavy chain (NM IIA cKO) and examined the structure and function of normal gut barrier, and the development of experimental colitis in these animals...
2016: Scientific Reports
K Hayakawa, A M Formica, M J Colombo, S A Shinton, J Brill-Dashoff, H C Morse Iii, Y-S Li, R R Hardy
A common feature of B-cell chronic lymphocytic leukemia (CLL) is chromosomal loss of 13q14, containing the miR15a/16-1 locus controlling B-cell proliferation. However, CLL etiology remains unclear. CLL is an adult leukemia with an incidence that increases with advancing age. A unique feature of CLL is biased B-cell antigen receptor (BCR) usage, autoreactivity with polyreactivity and CD5 expression, all suggest a role for the BCR in driving CLL pathogenesis. Among human CLLs, BCRs autoreactive with non-muscle myosin IIA (AMyIIA) are recurrent...
July 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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