Actin regulators take the reins in Drosophila myoblast fusion

2009 ◽  
Vol 4 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Susanne-Filiz Önel
Keyword(s):  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Myoblast Fusion ◽  
Fusion Pore ◽  
Specific Cell ◽  
Muscle Formation ◽  
Biochemical Analyses ◽  
Made In ◽  
Skeletal Muscle Formation

AbstractSkeletal muscle formation, growth and repair depend on myoblast fusion events. Therefore, in-depth understanding of the underlying molecular mechanisms controlling these events that ultimately lead to skeletal muscle formation may be fundamental for developing new therapies for tissue repair. To this end, the greatest advances in furthering understanding myoblast fusion has been made in Drosophila. Recent studies have shown that transient F-actin structures, so-called actin plugs or foci, are known to form at the site of contacting myoblasts. Indeed, actin regulators of the WASP family that control the activation of the Arp2/3 complex and thereby branched F-actin formation have been demonstrated to be crucial for myoblast fusion. Myoblast-specific cell adhesion molecules seem to be involved in the recruitment of WASP family members to the site of myoblast fusion and form a Fusion-Restricted Myogenic-Adhesive Structure (FuRMAS). Currently, the exact role of the FuRMAS is not completely understood. However, recent studies indicate that WASP-dependent F-actin regulation is required for fusion pore formation as well as for the correct integration of fusing myoblasts into the growing muscle. In this review, I discuss latest cellular studies, and recent genetic and biochemical analyses on actin regulation during myoblast fusion.

scholarly journals Signaling mechanism of myoblast fusion in skeletal muscle formation

2019 ◽  
Vol 92 (0) ◽  
pp. 1-S04-4
Author(s):  
Taichiro Tomida ◽  
Kimitaka Yamaguchi ◽  
Masanori Ito ◽  
Yoshinori Mikami ◽  
Daisuke Ohshima ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Myoblast Fusion ◽  
Signaling Mechanism ◽  
Muscle Formation ◽  
Skeletal Muscle Formation

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Number Of Genes ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
Genetic And Environmental Factors ◽  
Made In

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

scholarly journals Mechanosensitive Ion Channel Piezo1 Regulates Myocyte Fusion during Skeletal Myogenesis

2020 ◽  
Author(s):  
Huascar Pedro Ortuste Quiroga ◽  
Shingo Yokoyama ◽  
Massimo Ganassi ◽  
Kodai Nakamura ◽  
Tomohiro Yamashita ◽  
...  
Keyword(s):  
Ion Channel ◽  
Molecular Mechanisms ◽  
Myoblast Fusion ◽  
Mechanical Stimuli ◽  
Muscle Satellite Cell ◽  
Myotube Formation ◽  
Mechanosensitive Ion Channel ◽  
And Function ◽  
Sirna Knockdown

AbstractMechanical stimuli such as stretch and resistance training are essential to regulate growth and function of skeletal muscle. However, the molecular mechanisms involved in sensing mechanical stress remain unclear. Here, the purpose of this study was to investigate the role of the mechanosensitive ion channel Piezo1 during myogenic progression. Muscle satellite cell-derived myoblasts and myotubes were modified with stretch, siRNA knockdown and agonist-induced activation of Piezo1. Direct manipulation of Piezo1 modulates terminal myogenic progression. Piezo1 knockdown suppressed myoblast fusion during myotube formation and maturation. This was accompanied by downregulation of the fusogenic protein Myomaker. Piezo1 knockdown also lowered Ca2+ influx in response to stretch. Conversely Piezo1 activation stimulated fusion and increased Ca2+ influx in response to stretch. These evidences indicate that Piezo1 is essential for myotube formation and maturation, which may have implications for msucular dystrophy prevention through its role as a mechanosensitive Ca2+ channel.

PHD Domain Deletion Mutations of ASXL1 Promote Myeloid Leukemia Transformation Through Epigenetic Dysregulation and Inhibit Megakaryocytic Differentiation Through the Inactivation of FOSB in K562 Cells.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2393-2393 ◽  
Author(s):  
Rabindranath Bera ◽  
Der-Cherng Liang ◽  
Ming-Chun Chiu ◽  
Ying-Jung Huang ◽  
Sung-Tzu Liang ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Molecular Mechanisms ◽  
Blast Crisis ◽  
K562 Cells ◽  
Specific Cell ◽  
Wild Type ◽  
Megakaryocytic Differentiation ◽  
Deletion Mutations ◽  
Phd Domain

Abstract Abstract 2393 Somatic mutations of ASXL1 gene have been described in patients with myeloid malignancies and were associated with inferior outcomes. ASXL1 mutations have also been detected in myeloid blast crisis of chronic myeloid leukemia (CML) patients. The mechanisms of acute myeloid leukemia (AML) transformation and functional role of ASXL1 mutations in the leukemogenesis remain to be determined. Recently, we identified PHD domain deletion mutations (R693X and L885X) in patients with CML in myeloid blast crisis and/or AML with minimal differentiation (M0). In the present study, we aimed to investigate the role of PHD domain deletion mutations in the pathogenesis of AML transformation. The K562 cells carrying Philadelphia chromosome, serves as a model to study the molecular mechanisms associated with leukemogenesis. Our result showed that R693X/L885X mutations inhibited PMA-treated megakaryocytic differentiation with the change of physiological characteristic features and suppressed the induction of CD61, a specific cell surface marker of megakaryocytes. We also found that FOSB, a member of Fos family of AP-1 transcription factors was down-regulated in K562 cells expressing R693X and L885X compared to wild-type ASXL1 during PMA-mediated megakaryocytic differentiation. Examination of intracellular signaling pathways showed that the mutant ASXL1 protein prevented PMA-induced megakaryocytic differentiation through the inactivation of ERK, AKT and STAT5 which are required for differentiation. Further, ASXL1 depletion by shRNA in K562 cells led to enhanced cell proliferation, increased colony formation and impaired PMA-mediated differentiation. Previous studies in Drosophila had revealed that Asxl forms the protein complexes of both Trithorax and Polycomb groups that are required for maintaining chromatin in both activated and repressed transcriptional states. By using Western blot analysis, we demonstrated that PHD domain deletion mutations of ASXL1 significantly suppressed the transcriptionally repressive mark H3K27 trimethylation, however no effect on methylated H3K4 (H3K4me2 and H3K4me3), an active histone mark in K562 cells. Co-immunoprecipitation analysis revealed that wild-type, but not PHD domain deletion mutations of ASXL1 interact with EZH2, a member of the polycomb repressive complex 2 (PRC2). Importantly, PHD deletion mutations or downregulation of ASXL1 resulted in the suppression of EZH2 in K562 cells. Our study demonstrated that PHD deletion mutations of ASXL1 resulted in a loss-of-function which exhibited direct effects on the proliferation and differentiation and also proposed a specific role for ASXL1 in epigenetic regulation of gene expression in K562 cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Kidney disease associated with plasma cell dyscrasias

Blood ◽  
2010 ◽  
Vol 116 (9) ◽  
pp. 1397-1404 ◽  
Author(s):  
Eliot C. Heher ◽  
Nelson B. Goes ◽  
Thomas R. Spitzer ◽  
Noopur S. Raje ◽  
Benjamin D. Humphreys ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Plasma Cell ◽  
Molecular Mechanisms ◽  
Kidney Injury ◽  
Light Chains ◽  
Free Light Chains ◽  
Monoclonal Immunoglobulin ◽  
Plasma Cell Dyscrasias ◽  
Made In

Plasma cell dyscrasias are frequently encountered malignancies often associated with kidney disease through the production of monoclonal immunoglobulin (Ig). Paraproteins can cause a remarkably diverse set of pathologic patterns in the kidney and recent progress has been made in explaining the molecular mechanisms of paraprotein-mediated kidney injury. Other recent advances in the field include the introduction of an assay for free light chains and the use of novel antiplasma cell agents that can reverse renal failure in some cases. The role of stem cell transplantation, plasma exchange, and kidney transplantation in the management of patients with paraprotein-related kidney disease continues to evolve.

scholarly journals The Role of the Cyclin Dependent Kinase Inhibitor p21cip1/waf1 in Targeting Cancer: Molecular Mechanisms and Novel Therapeutics

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1475 ◽  
Author(s):  
Al Bitar ◽  
Gali-Muhtasib
Keyword(s):  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Kinase Inhibitor ◽  
Biological Activities ◽  
Cyclin Dependent Kinase ◽  
Cycle Progression ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Multiple Signaling ◽  
Made In

p21cip1/waf1 mediates various biological activities by sensing and responding to multiple stimuli, via p53-dependent and independent pathways. p21 is known to act as a tumor suppressor mainly by inhibiting cell cycle progression and allowing DNA repair. Significant advances have been made in elucidating the potential role of p21 in promoting tumorigenesis. Here, we discuss the involvement of p21 in multiple signaling pathways, its dual role in cancer, and the importance of understanding its paradoxical functions for effectively designing therapeutic strategies that could selectively inhibit its oncogenic activities, override resistance to therapy and yet preserve its tumor suppressive functions.

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