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Non muscle myosin IIA

Andrius Masedunskas, Mark A Appaduray, Christine A Lucas, María Lastra Cagigas, Marco Heydecker, Mira Holliday, Joyce Meiring, Jeff Hook, Anthony Kee, Melissa White, Paul Thomas, Yingfan Zhang, Robert S Adelstein, Tobias Meckel, Till Böcking, Roberto Weigert, Nicole S Bryce, Peter W Gunning, Edna C Hardeman
Many actin filaments in animal cells are co-polymers of actin and tropomyosin. For many of these co-polymers, non-muscle myosin II associates to establish a contractile network. However, the temporal relationship of these 3 proteins in the de novo assembly of actin filaments is not known. Intravital subcellular microscopy of secretory granule exocytosis allows the visualisation and quantitation of the formation of an actin scaffold in real time with the added advantage that it occurs in a living mammal, under physiological conditions...
February 27, 2018: Journal of Cell Science
Matthew J Brooks, Ameena Hajira, Junaith S Mohamed, Stephen E Alway
Reloading of atrophied muscles after hindlimb suspension unloading (HSU) can induce injury and prolong recovery. Low-impact exercise, such as voluntary wheel running, has been identified as a non-damaging rehabilitation therapy in rodents, but its effects on muscle function, morphology, and satellite cell activity after HSU are unclear. This study tested the hypothesis that low impact wheel running would increase satellite cell proliferation and improve recovery of muscle structure and function after HSU in mice...
February 22, 2018: Journal of Applied Physiology
Francisco Sarmento Mesquita, Cláudia Brito, Didier Cabanes, Sandra Sousa
Following damage by pore forming toxins (PFTs) host cells engage repair processes and display profound cytoskeletal remodeling and concomitant plasma membrane (PM) blebbing. We have recently demonstrated that host cells utilize similar mechanisms to control cytoskeletal dynamics in response to PFTs and during cell migration. This involves assembly of cortical actomyosin bundles, reorganisation of the endoplasmic reticulum (ER) network, and the interaction between the ER chaperone Gp96 and the molecular motor Non-muscle Myosin Heavy Chain IIA (NMHCIIA)...
2017: Communicative & Integrative Biology
Carolina P Gomez, Albert Descoteaux
Biogenesis of phagolysosomes is central to the elimination of pathogens by macrophages. We previously showed that Src homology region 2 domain-containing phosphatase 1 (SHP-1) participates in the regulation of phagosome maturation. Through proteomics, we identified moesin and the non-muscle myosin-IIA as proteins interacting with SHP-1 during phagocytosis. Silencing of either moesin or myosin IIA with small interfering RNA inhibited phagosomal acidification and recruitment of LAMP-1. Moreover, the intraphagosomal oxidative burst was impaired in the absence of either SHP-1 or myosin IIA but not moesin...
December 13, 2017: Biochemical and Biophysical Research Communications
Pin Li, Guoqin Wei, Yang Cao, Qiuping Deng, Xiaofan Han, Xiaoshuai Huang, Yingqing Huo, Yulong He, Liangyi Chen, Jincai Luo
Nonmuscle myosin II has been implicated in regulation of von Willebrand factor (VWF) release from endothelial Weibel-Palade bodies (WPBs), but the specific role of myosin IIa isoform is poorly defined. Here, we report that myosin IIa is expressed both in primary human endothelial cells and intact mouse vessels, essential for cyclic adenosine monophosphate (cAMP)-mediated endothelial VWF secretion. Downregulation of myosin IIa by shRNAs significantly suppressed both forskolin- and epinephrine-induced VWF secretion...
February 8, 2018: Blood
David J Rabbolini, Yenna Chun, Maya Latimer, Shinji Kunishima, Kathleen Fixter, Bhavia Valecha, Peter Tan, Lee Ping Chew, Benjamin T Kile, Rachel Burt, Kottayam Radhakrishnan, Robert Bird, Paul Ockelford, Sara Gabrielli, Qiang Chen, William S Stevenson, Christopher M Ward, Marie-Christine Morel-Kopp
MYH9-related disorders (MYH9-RDs) caused by mutation of the MYH9 gene which encodes non-muscle myosin heavy-chain-IIA (NMMHC-IIA), an important motor protein in hemopoietic cells, are the most commonly encountered cause of inherited macrothrombocytopenia. Despite distinguishing features including an autosomal dominant mode of inheritance, giant platelets on the peripheral blood film accompanied by leucocytes with cytoplasmic inclusion bodies (döhle-like bodies), these disorders remain generally under-recognized and often misdiagnosed as immune thrombocytopenia (ITP)...
November 1, 2017: Platelets
Yuanyuan Zhang, Yuwei Han, Yazheng Zhao, Yanni Lv, Yang Hu, Yisha Tan, Xueyuan Bi, Boyang Yu, Junping Kou
DT-13(25(R,S)-ruscogenin-1-O-[β-d-glucopyranosyl-(1→2)][β-d-xylopyranosyl-(1→3)]-β-d-fucopyranoside) has been identified as an important factor in TNF-α-induced vascular inflammation. However, the effect of DT-13 on TNF-α-induced endothelial permeability and the potential molecular mechanisms remain unclear. Hence, this study was undertaken to elucidate the protective effect of DT-13 on TNF-α-induced endothelial permeability and the underlying mechanisms in vivo and in vitro. The in vivo results showed that DT-13 could ameliorate endothelial permeability in mustard oil-induced plasma leakage in the skin and modulate ZO-1 organization...
2017: Frontiers in Immunology
Kim-Vy Nguyen-Ngoc, Vanesa L Silvestri, Dan Georgess, Amanda N Fairchild, Andrew J Ewald
The mammary epithelium elaborates through hormonally regulated changes in proliferation, migration and differentiation. Non-muscle myosin II (NMII) functions at the interface between contractility, adhesion and signal transduction. It is therefore a plausible regulator of mammary morphogenesis. We tested the genetic requirement for NMIIA and NMIIB in mammary morphogenesis through deletion of the three NMII heavy chain-encoding genes ( NMHCIIA , NMHCIIB and NMHCIIC ; also known as MYH9 , MYH10 and MYH14 , respectively) that confer specificity to the complex...
October 1, 2017: Journal of Cell Science
Taro Toyoda, Azuma Kimura, Hiromi Tanaka, Tomonaga Ameku, Atsushi Mima, Yurie Hirose, Masahiro Nakamura, Akira Watanabe, Kenji Osafune
There has been increasing success with the generation of pancreatic cells from human induced pluripotent stem cells (hiPSCs); however, the molecular mechanisms of the differentiation remain elusive. The purpose of this study was to reveal novel molecular mechanisms for differentiation to PDX1(+)NKX6.1(+) pancreatic endoderm cells, which are pancreatic committed progenitor cells. PDX1(+) posterior foregut cells differentiated from hiPSCs failed to differentiate into pancreatic endoderm cells at low cell density, but Rho-associated kinase (ROCK) or non-muscle myosin II (NM II) inhibitors rescued the differentiation potential...
August 8, 2017: Stem Cell Reports
Jiro Takito, Hirotada Otsuka, Satoshi Inoue, Tsubasa Kawashima, Masanori Nakamura
The aim of this study was to elucidate the role of the zipper-like structure (ZLS), a podosome-related structure that transiently appears at the cell contact zone, in osteoclast fusion. Live-cell imaging of osteoclasts derived from RAW264.7 cells transfected with EGFP-actin revealed consistent symmetrical retrograde actin flow in the ZLS, but not in the podosome cluster, the podosome ring or the podosome belt. Confocal imaging showed that the distributions of F-actin, vinculin, paxillin and zyxin in the ZLS were different from those in the podosome belt...
July 15, 2017: Biology Open
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
Yuanyuan Zhang, Long Li, Yazheng Zhao, Han Han, Yang Hu, Di Liang, Boyang Yu, Junping Kou
Arterial thrombosis and its related diseases are major healthcare problems worldwide. Blebbistatin is an inhibitor of myosin II, which plays an important role in thrombosis. The aim of our study is to explore the effect and potential mechanism of blebbistatin on arterial thrombosis. A ferric chloride (FeCl3) solution at a concentration of 5% was used to induce carotid artery thrombosis in mice. Immunohistochemistry and immunofluorescence staining were used to detect the expression or activation of non-muscle myosin heavy chain IIA (NMMHC IIA), tissue factor (TF), GSK3β and NF-κB...
2017: International Journal of Biological Sciences
Pamma D Arora, Madeleine Di Gregorio, Pei He, Christopher A McCulloch
Fibroblasts remodel extracellular matrix collagen, in part, through phagocytosis. This process requires formation of cell extensions, which in turn involves interaction of the actin-binding protein flightless-1 (FliI) with non-muscle myosin IIA (NMMIIA; heavy chain encoded by MYH9) at cell-matrix adhesion sites. As Ca(2+) plays a central role in controlling actomyosin-dependent functions, we examined how Ca(2+) controls the generation of cell extensions and collagen remodeling. Ratio fluorimetry demonstrated localized Ca(2+) influx at the extensions of fibroblasts...
July 1, 2017: Journal of Cell Science
Simon G Pfisterer, Gergana Gateva, Peter Horvath, Juho Pirhonen, Veijo T Salo, Leena Karhinen, Markku Varjosalo, Samppa J Ryhänen, Pekka Lappalainen, Elina Ikonen
Lipid droplets (LDs) are cellular organelles specialized in triacylglycerol (TG) storage undergoing homotypic clustering and fusion. In non-adipocytic cells with numerous LDs this is balanced by poorly understood droplet dissociation mechanisms. We identify non-muscle myosin IIa (NMIIa/MYH-9) and formin-like 1 (FMNL1) in the LD proteome. NMIIa and actin filaments concentrate around LDs, and form transient foci between dissociating LDs. NMIIa depletion results in decreased LD dissociations, enlarged LDs, decreased hydrolysis and increased storage of TGs...
March 31, 2017: Nature Communications
Shixin Zhou, Yinan Liu, Yumin Ma, Xiaoyan Zhang, Yang Li, Jinhua Wen
Human embryonic stem cells (hESCs) are a unique population of cells defined by their capacity for self-renewal and pluripotency. Here, we identified a previously uncharacterized gene in hESCs, C9ORF135, which is sharply downregulated during gastrulation and gametogenesis, along with the pluripotency factors OCT4, SOX2, and NANOG. Human ESCs express two C9ORF135 isoforms, the longer of which encodes a membrane-associated protein, as determined by immunostaining and western blotting of fractionated cell lysates...
March 27, 2017: Scientific Reports
Wenwu Zhang, Susan J Gunst
KEY POINTS: Non-muscle (NM) and smooth muscle (SM) myosin II are both expressed in smooth muscle tissues, however the role of NM myosin in SM contraction is unknown. Contractile stimulation of tracheal smooth muscle tissues stimulates phosphorylation of the NM myosin heavy chain on Ser1943 and causes NM myosin filament assembly at the SM cell cortex. Expression of a non-phosphorylatable NM myosin mutant, NM myosin S1943A, in SM tissues inhibits ACh-induced NM myosin filament assembly and SM contraction, and also inhibits the assembly of membrane adhesome complexes during contractile stimulation...
July 1, 2017: Journal of Physiology
Gergana Gateva, Elena Kremneva, Theresia Reindl, Tommi Kotila, Konstantin Kogan, Laurène Gressin, Peter W Gunning, Dietmar J Manstein, Alphée Michelot, Pekka Lappalainen
Actin filaments assemble into a variety of networks to provide force for diverse cellular processes [1]. Tropomyosins are coiled-coil dimers that form head-to-tail polymers along actin filaments and regulate interactions of other proteins, including actin-depolymerizing factor (ADF)/cofilins and myosins, with actin [2-5]. In mammals, >40 tropomyosin isoforms can be generated through alternative splicing from four tropomyosin genes. Different isoforms display non-redundant functions and partially non-overlapping localization patterns, for example within the stress fiber network [6, 7]...
March 6, 2017: Current Biology: CB
Nuno M Coelho, Pamma D Arora, Sander van Putten, Stellar Boo, Petar Petrovic, Alyna Xue Lin, Boris Hinz, Christopher A McCulloch
Discoidin domain receptor 1 (DDR1) is a tyrosine kinase collagen adhesion receptor that mediates cell migration through association with non-muscle myosin IIA (NMIIA). Because DDR1 is implicated in cancer fibrosis, we hypothesized that DDR1 interacts with NMIIA to enable collagen compaction by traction forces. Mechanical splinting of rat dermal wounds increased DDR1 expression and collagen alignment. In periodontal ligament of DDR1 knockout mice, collagen mechanical reorganization was reduced >30%. Similarly, cultured cells with DDR1 knockdown or expressing kinase-deficient DDR1d showed 50% reduction of aligned collagen...
February 14, 2017: Cell Reports
Sonya D Coaxum, Jessica Tiedeken, Elizabeth Garrett-Mayer, Jeffrey Myers, Steven A Rosenzweig, David M Neskey
Over 300,000 patients develop squamous cell carcinoma of the head and neck (HNSCC) worldwide with 25-30% of patients ultimately dying from their disease. Currently, molecular biomarkers are not used in HNSCC but several genes have been identified including mutant TP53 (mutp53). Our recent work has identified an approach to stratify patients with tumors harboring high or low risk TP53 mutations. Non-muscle Myosin IIA (NMIIA) was recently identified as a tumor suppressor in HNSCC. We now demonstrate that low MYH9 expression is associated with decreased survival in patients with head and neck cancer harboring low-risk mutp53 but not high-risk mutp53...
April 4, 2017: Oncotarget
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...
February 2017: EMBO Reports
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