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The Journal of General Physiology Nov 2023JGP study (In this issue, Osten et al. https://doi.org/10.1085/jgp.202313377) suggests that, by altering mechanosensitive signaling pathways, replating stem cell-derived...
JGP study (In this issue, Osten et al. https://doi.org/10.1085/jgp.202313377) suggests that, by altering mechanosensitive signaling pathways, replating stem cell-derived cardiomyocytes changes myosin expression and contractile function.
Topics: Muscle Contraction; Myosins; Signal Transduction
PubMed: 37847309
DOI: 10.1085/jgp.202313491 -
The EMBO Journal Aug 2023The scaffolding protein angiomotin (AMOT) is indispensable for vertebrate embryonic angiogenesis. Here, we report that AMOT undergoes cleavage in the presence of...
The scaffolding protein angiomotin (AMOT) is indispensable for vertebrate embryonic angiogenesis. Here, we report that AMOT undergoes cleavage in the presence of lysophosphatidic acid (LPA), a lipid growth factor also involved in angiogenesis. AMOT cleavage is mediated by aspartic protease DNA damage-inducible 1 homolog 2 (DDI2), and the process is tightly regulated by a signaling axis including neurofibromin 2 (NF2), tankyrase 1/2 (TNKS1/2), and RING finger protein 146 (RNF146), which induce AMOT membrane localization, poly ADP ribosylation, and ubiquitination, respectively. In both zebrafish and mice, the genetic inactivation of AMOT cleavage regulators leads to defective angiogenesis, and the phenotype is rescued by the overexpression of AMOT-CT, a C-terminal AMOT cleavage product. In either physiological or pathological angiogenesis, AMOT-CT is required for vascular expansion, whereas uncleavable AMOT represses this process. Thus, our work uncovers a signaling pathway that regulates angiogenesis by modulating a cleavage-dependent activation of AMOT.
Topics: Animals; Mice; Angiomotins; Zebrafish; Microfilament Proteins; Peptide Hydrolases; Intercellular Signaling Peptides and Proteins
PubMed: 37350545
DOI: 10.15252/embj.2022112900 -
Cells Oct 2023Maintenance of skeletal muscle quantity and quality is essential to ensure various vital functions of the body. Muscle homeostasis is regulated by multiple cytoskeletal... (Review)
Review
Maintenance of skeletal muscle quantity and quality is essential to ensure various vital functions of the body. Muscle homeostasis is regulated by multiple cytoskeletal proteins and myogenic transcriptional programs responding to endogenous and exogenous signals influencing cell structure and function. Since actin is an essential component in cytoskeleton dynamics, actin-binding proteins (ABPs) have been recognized as crucial players in skeletal muscle health and diseases. Hence, dysregulation of ABPs leads to muscle atrophy characterized by loss of mass, strength, quality, and capacity for regeneration. This comprehensive review summarizes the recent studies that have unveiled the role of ABPs in actin cytoskeletal dynamics, with a particular focus on skeletal myogenesis and diseases. This provides insight into the molecular mechanisms that regulate skeletal myogenesis via ABPs as well as research avenues to identify potential therapeutic targets. Moreover, this review explores the implications of non-coding RNAs (ncRNAs) targeting ABPs in skeletal myogenesis and disorders based on recent achievements in ncRNA research. The studies presented here will enhance our understanding of the functional significance of ABPs and mechanotransduction-derived myogenic regulatory mechanisms. Furthermore, revealing how ncRNAs regulate ABPs will allow diverse therapeutic approaches for skeletal muscle disorders to be developed.
Topics: Microfilament Proteins; Actins; Mechanotransduction, Cellular; Muscle, Skeletal; RNA, Untranslated; Muscle Development
PubMed: 37947600
DOI: 10.3390/cells12212523 -
Expert Review of Cardiovascular Therapy 2023
Topics: Humans; Cardiac Surgical Procedures; Myocardial Infarction; Troponin; Biomarkers; Troponin T; Postoperative Complications
PubMed: 37947177
DOI: 10.1080/14779072.2023.2283123 -
JAMA Cardiology Sep 2023
Topics: Pregnancy; Female; Humans; Troponin T; Troponin I
PubMed: 37494028
DOI: 10.1001/jamacardio.2023.2109 -
JAMA Cardiology Sep 2023
Topics: Humans; Pregnancy; Female; Troponin; Troponin T; Myocardial Infarction
PubMed: 37494021
DOI: 10.1001/jamacardio.2023.2112 -
Cell Death & Disease Aug 2023WWC1 regulates episodic learning and memory, and genetic nucleotide polymorphism of WWC1 is associated with neurodegenerative diseases such as Alzheimer's disease....
WWC1 regulates episodic learning and memory, and genetic nucleotide polymorphism of WWC1 is associated with neurodegenerative diseases such as Alzheimer's disease. However, the molecular mechanism through which WWC1 regulates neuronal function has not been fully elucidated. Here, we show that WWC1 and its paralogs (WWC2/3) bind directly to angiomotin (AMOT) family proteins (Motins), and recruit USP9X to deubiquitinate and stabilize Motins. Deletion of WWC genes in different cell types leads to reduced protein levels of Motins. In mice, neuron-specific deletion of Wwc1 and Wwc2 results in reduced expression of Motins and lower density of dendritic spines in the cortex and hippocampus, in association with impaired cognitive functions such as memory and learning. Interestingly, ectopic expression of AMOT partially rescues the neuronal phenotypes associated with Wwc1/2 deletion. Thus, WWC proteins modulate spinogenesis and cognition, at least in part, by regulating the protein stability of Motins.
Topics: Mice; Animals; Angiomotins; Learning; Hippocampus; Neurons; Microfilament Proteins; Cognition
PubMed: 37528078
DOI: 10.1038/s41419-023-06020-7 -
Proceedings of the National Academy of... Sep 2023The shape of cells is the outcome of the balance of inner forces produced by the actomyosin network and the resistive forces produced by cell adhesion to their...
The shape of cells is the outcome of the balance of inner forces produced by the actomyosin network and the resistive forces produced by cell adhesion to their environment. The specific contributions of contractile, anchoring and friction forces to network deformation rate and orientation are difficult to disentangle in living cells where they influence each other. Here, we reconstituted contractile actomyosin networks in vitro to study specifically the role of the friction forces between the network and its anchoring substrate. To modulate the magnitude and spatial distribution of friction forces, we used glass or lipids surface micropatterning to control the initial shape of the network. We adapted the concentration of Nucleating Promoting Factor on each surface to induce the assembly of actin networks of similar densities and compare the deformation of the network toward the centroid of the pattern shape upon myosin-induced contraction. We found that actin network deformation was faster and more coordinated on lipid bilayers than on glass, showing the resistance of friction to network contraction. To further study the role of the spatial distribution of these friction forces, we designed heterogeneous micropatterns made of glass and lipids. The deformation upon contraction was no longer symmetric but biased toward the region of higher friction. Furthermore, we showed that the pattern of friction could robustly drive network contraction and dominate the contribution of asymmetric distributions of myosins. Therefore, we demonstrate that during contraction, both the active and resistive forces are essential to direct the actin network deformation.
Topics: Actins; Friction; Actomyosin; Muscle Contraction; Lipid Bilayers
PubMed: 37725653
DOI: 10.1073/pnas.2300416120 -
Cancer Genomics & Proteomics 2023Mesotheliomas are tumors similar to, and probably derived from, mesothelial cells. They carry acquired chromosomal rearrangements, deletions affecting CDKN2A,...
BACKGROUND/AIM
Mesotheliomas are tumors similar to, and probably derived from, mesothelial cells. They carry acquired chromosomal rearrangements, deletions affecting CDKN2A, pathogenetic polymorphisms in NF2, and fusion genes which often contain the promiscuous EWSR1, FUS, and ALK as partner genes. Here, we report the cytogenomic results on two peritoneal mesotheliomas.
MATERIALS AND METHODS
Both tumors were examined using G-banding with karyotyping and array comparative genomic hybridization (aCGH). One of them was further investigated with RNA sequencing, reverse transcription polymerase chain reaction (RT-PCR), Sanger sequencing, and fluorescence in situ hybridization (FISH).
RESULTS
In the first mesothelioma, the karyotype was 25∼26,X,+5,+7,+20[cp4]/50∼52,idemx2[cp7]/46,XX[2]. aCGH detected gains of chromosomes 5, 7, and 20 with retained heterozygosity on these chromosomes. In the second tumor, the karyotype was 46,XX,inv(10)(p11q25)[7]/46,XX[3]. aCGH did not detect any gains or losses and showed heterozygosity for all chromosomes. RNA sequencing, RT-PCR/Sanger sequencing, and FISH showed that the inv(10) fused MAP3K8 from 10p11 with ABLIM1 from 10q25. The MAP3K8::ABLIM1 chimera lacked exon 9 of MAP3K8.
CONCLUSION
Our data, together with information on previously described mesotheliomas, illustrate two pathogenetic mechanisms in peritoneal mesothelioma: One pathway is characterized by hyperhaploidy, but with retained disomies for chromosomes 5, 7, and 20; this may be particularly prevalent in biphasic mesotheliomas. The second pathway is characterized by rearrangements of MAP3K8 from which exon 9 of MAP3K8 is lost. The absence of exon 9 from oncogenetically rearranged MAP3K8 is a common theme in thyroid carcinoma, lung cancer, and spitzoid as well as other melanoma subtypes.
Topics: Humans; In Situ Hybridization, Fluorescence; Comparative Genomic Hybridization; Mesothelioma, Malignant; Mesothelioma; Carcinogenesis; Cell Transformation, Neoplastic; Peritoneal Neoplasms; Microfilament Proteins; LIM Domain Proteins
PubMed: 37400148
DOI: 10.21873/cgp.20388 -
Progress in Lipid Research Jul 2023Adipokines play a significant role in cardiometabolic diseases. Asprosin, a newly discovered adipokine, was first identified as a glucose-raising protein hormone.... (Review)
Review
Adipokines play a significant role in cardiometabolic diseases. Asprosin, a newly discovered adipokine, was first identified as a glucose-raising protein hormone. Asprosin also stimulates appetite and regulates glucose and lipid metabolism. Its identified receptors so far include Olfr734 and Ptprd. Clinical studies have found that asprosin may be associated with cardiometabolic diseases. Asprosin may have diagnostic and therapeutic potential in obesity, diabetes, metabolic syndrome and atherosclerotic cardiovascular diseases. Herein, the structure, receptors, and functions of asprosin and its relationship with cardiometabolic diseases are summarized based on recent findings.
Topics: Humans; Adipokines; Cardiovascular Diseases; Peptide Hormones; Microfilament Proteins; Peptide Fragments; Fibrillin-1; Glucose
PubMed: 37473965
DOI: 10.1016/j.plipres.2023.101240