scholarly journals The Sarcomeric M-Region: A Molecular Command Center for Diverse Cellular Processes

2015 ◽  
Vol 2015 ◽  
pp. 1-25 ◽  
Author(s):  
Li-Yen R. Hu ◽  
Maegen A. Ackermann ◽  
Aikaterini Kontrogianni-Konstantopoulos
Keyword(s):  
Signal Transduction ◽  
Thick Filament ◽  
Cellular Processes ◽  
Cytoskeletal Remodeling ◽  
Filament Assembly ◽  
Thick Filaments ◽  
Genes Encoding ◽  
Related Proteins ◽  
Command Center

The sarcomeric M-region anchors thick filaments and withstands the mechanical stress of contractions by deformation, thus enabling distribution of physiological forces along the length of thick filaments. While the role of the M-region in supporting myofibrillar structure and contractility is well established, its role in mediating additional cellular processes has only recently started to emerge. As such, M-region is the hub of key protein players contributing to cytoskeletal remodeling, signal transduction, mechanosensing, metabolism, and proteasomal degradation. Mutations in genes encoding M-region related proteins lead to development of severe and lethal cardiac and skeletal myopathies affecting mankind. Herein, we describe the main cellular processes taking place at the M-region, other than thick filament assembly, and discuss human myopathies associated with mutant or truncated M-region proteins.

scholarly journals Hydrophobicity variations along the surface of the coiled-coil rod may mediate striated muscle myosin assembly in Caenorhabditis elegans.

1996 ◽  
Vol 135 (2) ◽  
pp. 371-382 ◽  
Author(s):  
P E Hoppe ◽  
R H Waterston
Keyword(s):  
Caenorhabditis Elegans ◽  
Striated Muscle ◽  
Coiled Coil ◽  
Thick Filament ◽  
Surface Hydrophobicity ◽  
Filament Assembly ◽  
Thick Filaments ◽  
Characteristic Variation ◽  
Muscle Myosin

Caenorhabditis elegans body wall muscle contains two isoforms of myosin heavy chain, MHC A and MHC B, that differ in their ability to initiate thick filament assembly. Whereas mutant animals that lack the major isoform, MHC B, have fewer thick filaments, mutant animals that lack the minor isoform, MHC A, contain no normal thick filaments. MHC A, but not MHC B, is present at the center of the bipolar thick filament where initiation of assembly is thought to occur (Miller, D.M.,I. Ortiz, G.C. Berliner, and H.F. Epstein. 1983. Cell. 34:477-490). We mapped the sequences that confer A-specific function by constructing chimeric myosins and testing them in vivo. We have identified two distinct regions of the MHC A rod that are sufficient in chimeric myosins for filament initiation function. Within these regions, MHC A displays a more hydrophobic rod surface, making it more similar to paramyosin, which forms the thick filament core. We propose that these regions play an important role in filament initiation, perhaps mediating close contacts between MHC A and paramyosin in an antiparallel arrangement at the filament center. Furthermore, our analysis revealed that all striated muscle myosins show a characteristic variation in surface hydrophobicity along the length of the rod that may play an important role in driving assembly and determining the stagger at which dimers associate.

scholarly journals A Structural Model for Phosphorylation Control of Dictyostelium Myosin II Thick Filament Assembly

1999 ◽  
Vol 147 (5) ◽  
pp. 1039-1048 ◽  
Author(s):  
Wenchuan Liang ◽  
Hans M. Warrick ◽  
James A. Spudich
Keyword(s):  
Structural Model ◽  
Myosin Ii ◽  
Coiled Coil ◽  
Thick Filament ◽  
Tail Region ◽  
Filament Assembly ◽  
Dictyostelium Myosin ◽  
Thick Filaments ◽  
Coil Structure

Myosin II thick filament assembly in Dictyostelium is regulated by phosphorylation at three threonines in the tail region of the molecule. Converting these three threonines to aspartates (3×Asp myosin II), which mimics the phosphorylated state, inhibits filament assembly in vitro, and 3×Asp myosin II fails to rescue myosin II–null phenotypes. Here we report a suppressor screen of Dictyostelium myosin II–null cells containing 3×Asp myosin II, which reveals a 21-kD region in the tail that is critical for the phosphorylation control. These data, combined with new structural evidence from electron microscopy and sequence analyses, provide evidence that thick filament assembly control involves the folding of myosin II into a bent monomer, which is unable to incorporate into thick filaments. The data are consistent with a structural model for the bent monomer in which two specific regions of the tail interact to form an antiparallel tetrameric coiled–coil structure.

Regulation of hemidesmosome dynamics and cell signaling by integrin α6β4

2021 ◽  
Vol 134 (18) ◽  
Author(s):  
Lisa te Molder ◽  
Jose M. de Pereda ◽  
Arnoud Sonnenberg
Keyword(s):  
Signal Transduction ◽  
Extracellular Matrix ◽  
Cell Adhesion ◽  
Epithelial Cells ◽  
Basement Membrane ◽  
Molecular Mechanisms ◽  
Vital Role ◽  
Cellular Processes ◽  
Integrin Α6β4

ABSTRACT Hemidesmosomes (HDs) are specialized multiprotein complexes that connect the keratin cytoskeleton of epithelial cells to the extracellular matrix (ECM). In the skin, these complexes provide stable adhesion of basal keratinocytes to the underlying basement membrane. Integrin α6β4 is a receptor for laminins and plays a vital role in mediating cell adhesion by initiating the assembly of HDs. In addition, α6β4 has been implicated in signal transduction events that regulate diverse cellular processes, including proliferation and survival. In this Review, we detail the role of α6β4 in HD assembly and beyond, and we discuss the molecular mechanisms that regulate its function.

scholarly journals Caenorhabditis elegans Unc-45 Is a Component of Muscle Thick Filaments and Colocalizes with Myosin Heavy Chain B, but Not Myosin Heavy Chain a

2000 ◽  
Vol 148 (2) ◽  
pp. 375-384 ◽  
Author(s):  
Wanyuan Ao ◽  
Dave Pilgrim
Keyword(s):  
Caenorhabditis Elegans ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Body Wall ◽  
Thick Filament ◽  
The Body ◽  
Temperature Sensitive ◽  
Filament Assembly ◽  
Thick Filaments ◽  
Body Wall Muscles

In the nematode Caenorhabditis elegans, animals mutant in the gene encoding the protein product of the unc-45 gene (UNC-45) have disorganized muscle thick filaments in body wall muscles. Although UNC-45 contains tetratricopeptide repeats (TPR) as well as limited similarity to fungal proteins, no biochemical role has yet been found. UNC-45 reporters are expressed exclusively in muscle cells, and a functional reporter fusion is localized in the body wall muscles in a pattern identical to thick filament A-bands. UNC-45 colocalizes with myosin heavy chain (MHC) B in wild-type worms as well as in temperature-sensitive (ts) unc-45 mutants, but not in a mutant in which MHC B is absent. Surprisingly, UNC-45 localization is also not seen in MHC B mutants, in which the level of MHC A is increased, resulting in near-normal muscle thick filament structure. Thus, filament assembly can be independent of UNC-45. UNC-45 shows a localization pattern identical to and dependent on MHC B and a function that appears to be MHC B–dependent. We propose that UNC-45 is a peripheral component of muscle thick filaments due to its localization with MHC B. The role of UNC-45 in thick filament assembly seems restricted to a cofactor for assembly or stabilization of MHC B.

scholarly journals Dependence of expression of genes controlling calcium signaling on gravistimulation in cells of tomato apical leaves and treatment by etephon

2021 ◽  
Vol 65 (4) ◽  
pp. 456-465
Author(s):  
S. V. Sukhaveyeva ◽  
A. М. Kаbachevskaya ◽  
I. D. Volotovski
Keyword(s):  
Signal Transduction ◽  
Calcium Signaling ◽  
Calcium Metabolism ◽  
Early Response ◽  
Calcium Signal ◽  
Rt Pcr ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Exogenous Ethylene

The sensitivity of expression at the level of transcription of genes encoding proteins involved in calcium signal transduction to gravistimulation was revealed using real-time RT-PCR. For three genes SCA2, РВР2, САМ2, the increase in the transcript formation was shown at early response stages, starting from 15–60 minute gravistimulus. The treatment of plants before the start of gravistimulation with an ethephon (source of exogenous ethylene) led to a change in the modulation of expression of the studied genes in response to gravistimulus. The role of calcium metabolism in realization of final steps of gravitropism reaction is considered.

scholarly journals A tumor suppressive long noncoding RNA, DRAIC, inhibits protein translation and induces autophagy by activating AMPK

2021 ◽  
Author(s):  
Shekhar Saha ◽  
Ying Zhang ◽  
Briana Wilson ◽  
Roger Abounader ◽  
Anindya Dutta
Keyword(s):  
Signal Transduction ◽  
Noncoding Rna ◽  
Protein Translation ◽  
Signal Transduction Pathways ◽  
Cellular Processes ◽  
Rna Transcripts ◽  
Castration Resistant ◽  
Iκb Kinase ◽  
Downstream Effects

LncRNAs are long RNA transcripts that do not code for proteins and that have been shown to play a major role in cellular processes through diverse mechanisms. DRAIC, a lncRNA which is downregulated in castration-resistant advanced prostate cancer, inhibits the NF-kB pathway by inhibiting the IκB kinase. Decreased DRAIC expression predicted poor patient outcome in gliomas and seven other cancers. We now report that DRAIC suppresses invasion, migration, colony formation and xenograft growth of glioblastoma derived cell lines. DRAIC activates AMPK by downregulating the NF-κB target gene GLUT1, and thus represses mTOR, leading to downstream effects such as decrease in protein translation and increase in autophagy. DRAIC, therefore, has an effect on multiple signal transduction pathways that are important for oncogenesis: the NF-κB pathway and AMPK-mTOR-S6K/ULK1 pathway. The regulation of NF-κB, protein translation and autophagy by the same lncRNA explains the tumor suppressive role of DRAIC in different cancers and reinforces the importance of lncRNAs as emerging regulators of signal transduction pathways.

scholarly journals Myosin and paramyosin are organized about a newly identified core structure.

1985 ◽  
Vol 100 (3) ◽  
pp. 904-915 ◽  
Author(s):  
H F Epstein ◽  
D M Miller ◽  
I Ortiz ◽  
G C Berliner
Keyword(s):  
Thick Filament ◽  
Core Structure ◽  
Polar Regions ◽  
Myosin Isoforms ◽  
The Core ◽  
Filament Assembly ◽  
Thick Filaments ◽  
Filament Structure ◽  
Intermediate Domain

Myosin isoforms A and B are differentially localized to the central and polar regions, respectively, of thick filaments in body wall muscle cells of Caenorhabditis elegans (Miller, D. M. III, I. Ortiz, G. C. Berliner, and H. F. Epstein, 1983, Cell, 34:477-490). Biochemical and electron microscope studies of KCl-dissociated filaments show that the myosin isoforms occupy a surface domain, paramyosin constitutes an intermediate domain, and a newly identified core structure exists. The diameters of the thick filaments vary significantly from 33.4 nm centrally to 14.0 nm near the ends. The latter value is comparable to the 15.2 nm diameter of the core structures. The internal density of the filament core appears solid medially and hollow at the poles. The differentiation of thick filament structure into supramolecular domains possessing specific substructures of characteristic stabilities suggests a sequential mode for thick filament assembly. In this model, the two myosin isoforms have distinct roles in assembly. The behavior of the myosins, including nucleation of assembly and determination of filament length, depend upon paramyosin and the core structure as well as their intrinsic molecular properties.

scholarly journals A tumor suppressive long noncoding RNA, DRAIC, inhibits protein translation and induces autophagy by activating AMPK

2021 ◽  
Author(s):  
Shekhar Saha ◽  
Ying Zhang ◽  
Briana Wilson ◽  
Roger Abounader ◽  
Anindya Dutta
Keyword(s):  
Signal Transduction ◽  
Noncoding Rna ◽  
Target Gene ◽  
Protein Translation ◽  
Signal Transduction Pathways ◽  
Cellular Processes ◽  
Rna Transcripts ◽  
Castration Resistant ◽  
Downstream Effects

LncRNAs are long RNA transcripts that do not code for proteins and that have been shown to play a major role in cellular processes through diverse mechanisms. DRAIC, a lncRNA which is downregulated in castration-resistant advanced prostate cancer, inhibits the NF-κB pathway by inhibiting the IκBαkinase. Decreased DRAIC expression predicted poor patient outcome in gliomas and seven other cancers. We now report that DRAIC suppresses invasion, migration, colony formation and xenograft growth of glioblastoma derived cell lines. DRAIC activates AMPK by downregulating the NF-κB target gene GLUT1, and thus represses mTOR, leading to downstream effects such as decrease in protein translation and increase in autophagy. DRAIC, therefore, has an effect on multiple signal transduction pathways that are important for oncogenesis: the NF-κB pathway and AMPK-mTOR-S6K/ULK1 pathway. The regulation of NF-κB, protein translation and autophagy by the same lncRNA explains the tumor suppressive role of DRAIC in different cancers and reinforces the importance of lncRNAs as emerging regulators of signal transduction pathways.

scholarly journals Caenorhabditis elegansUNC-96 Is a New Component of M-Lines That Interacts with UNC-98 and Paramyosin and Is Required in Adult Muscle for Assembly and/or Maintenance of Thick Filaments

2006 ◽  
Vol 17 (9) ◽  
pp. 3832-3847 ◽  
Author(s):  
Kristina B. Mercer ◽  
Rachel K. Miller ◽  
Tina L. Tinley ◽  
Seema Sheth ◽  
Hiroshi Qadota ◽  
...  
Keyword(s):  
Body Wall ◽  
Polarized Light ◽  
Thick Filament ◽  
Immunofluorescent Staining ◽  
Molecular Architecture ◽  
Adult Muscle ◽  
Filament Assembly ◽  
Thick Filaments ◽  
Reduced Temperature ◽  
Insight Into

To gain further insight into the molecular architecture, assembly, and maintenance of the sarcomere, we have carried out a molecular analysis of the UNC-96 protein in the muscle of Caenorhabditis elegans. By polarized light microscopy of body wall muscle, unc-96 mutants display reduced myofibrillar organization and characteristic birefringent “needles.” By immunofluorescent staining of known myofibril components, unc-96 mutants show major defects in the organization of M-lines and in the localization of a major thick filament component, paramyosin. In unc-96 mutants, the birefringent needles, which contain both UNC-98 and paramyosin, can be suppressed by starvation or by exposure to reduced temperature. UNC-96 is a novel ∼47-kDa polypeptide that has no recognizable domains. Antibodies generated to UNC-96 localize the protein to the M-line, a region of the sarcomere in which thick filaments are cross-linked. By genetic and biochemical criteria, UNC-96 interacts with UNC-98, a previously described component of M-lines, and paramyosin. Additionally, UNC-96 copurifies with native thick filaments. A model is presented in which UNC-96 is required in adult muscle to promote thick filament assembly and/or maintenance.

scholarly journals Genetic Analysis of Spirochete Flagellin Proteins and Their Involvement in Motility, Filament Assembly, and Flagellar Morphology

2008 ◽  
Vol 190 (16) ◽  
pp. 5607-5615 ◽  
Author(s):  
Chunhao Li ◽  
Charles W. Wolgemuth ◽  
Michael Marko ◽  
David G. Morgan ◽  
Nyles W. Charon
Keyword(s):  
Swimming Speed ◽  
Multidisciplinary Approach ◽  
Genetic Model ◽  
Protein Composition ◽  
Linear Elasticity Theory ◽  
Filament Assembly ◽  
Core Proteins ◽  
Periplasmic Flagella ◽  
Related Proteins

ABSTRACT The filaments of spirochete periplasmic flagella (PFs) have a unique structure and protein composition. In most spirochetes, the PFs consist of a core of at least three related proteins (FlaB1, FlaB2, and FlaB3) and a sheath of FlaA protein. The functions of these filament proteins remain unknown. In this study, we used a multidisciplinary approach to examine the role of these proteins in determining the composition, shape, and stiffness of the PFs and how these proteins impact motility by using the spirochete Brachyspira (formerly Treponema, Serpulina) hyodysenteriae as a genetic model. A series of double mutants lacking combinations of these PF proteins was constructed and analyzed. The results show the following. First, the diameters of PFs are primarily determined by the sheath protein FlaA, and that FlaA can form a sheath in the absence of an intact PF core. Although the sheath is important to the PF structure and motility, it is not essential. Second, the three core proteins play unequal roles in determining PF structure and swimming speed. The functions of the core proteins FlaB1 and FlaB2 overlap such that either one of these proteins is essential for the spirochete to maintain the intact PF structure and for cell motility. Finally, linear elasticity theory indicates that flagellar stiffness directly affects the spirochete's swimming speed.

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