scholarly journals The roles of grouper clathrin light chains in regulating the infection of a novel marine DNA virus, Singapore grouper iridovirus

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Liqun Wang ◽  
Qiang Li ◽  
Songwei Ni ◽  
Youhua Huang ◽  
Jingguang Wei ◽  
...  
Keyword(s):  
Virus Infection ◽  
Light Chains ◽  
Dna Virus ◽  
Virus Attachment ◽  
Heavy Chains ◽  
Fish Virus ◽  
Early Endosomes ◽  
Epinephelus Akaara ◽  
First Time

Abstract Clathrins, composed of clathrin heavy chains (CHCs) and clathrin light chains (CLCs), are usually hijacked by viruses for infection. However, the role of CLCs, especially in regulating fish virus infection, remains poorly understood. Here, two isoforms of CLCs were cloned from the red-spotted grouper (Epinephelus akaara) (EaCLCa and EaCLCb). Both EaCLC transcripts were expressed in all examined tissues, and the expression of EaCLCa was much higher than that of EaCLCb. Over-expressing EaCLCa-W119R mutant significantly reduced Singapore grouper iridovirus (SGIV) infectivity. However, no effect of EaCLCb-W122R on SGIV infection was observed. The detailed steps were further studied, mainly including virus attachment, entry and the following transport to early endosomes. EaCLCa-W119R mutant notably inhibited internalization of SGIV particles with no effect on SGIV attachment. Furthermore, EaCLCa-W119R mutant obviously impaired the delivery of SGIV to early endosomes after virus internalization. In addition, the EaCLCa-W119R mutant markedly reduced the colocalization of SGIV and actin. However, EaCLCb is not required for such events during SGIV infection. Taken together, these results demonstrate for the first time that EaCLCa and EaCLCb exerted different impacts on iridovirus infection, providing a better understanding of the mechanisms of SGIV infection and opportunities for the design of new antiviral strategies.

scholarly journals Role of Clathrin Light Chains in Regulating Invadopodia Formation

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 451
Author(s):  
Markus Mukenhirn ◽  
Francesco Muraca ◽  
Delia Bucher ◽  
Edgar Asberger ◽  
Elisa Cappio Barazzone ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Matrix Proteins ◽  
Light Chains ◽  
Heavy Chains ◽  
Uptake Pathway ◽  
The Matrix ◽  
Main Protein ◽  
First Time ◽  
Invadopodia Formation

One of the most fundamental processes of the cell is the uptake of molecules from the surrounding environment. Clathrin-mediated endocytosis (CME) is the best-described uptake pathway and regulates nutrient uptake, protein and lipid turnover at the plasma membrane (PM), cell signaling, cell motility and cell polarity. The main protein in CME is clathrin, which assembles as a triskelion-looking building block made of three clathrin heavy chains and three clathrin light chains. Compared to clathrin heavy chains (CHCs), the role of the two isoforms of clathrin light chains (CLCA and CLCB) is poorly understood. Here, we confirm that the simultaneous deletion of both CLCA/B causes abnormal actin structures at the ventral PM and we describe them, for the first time, as functional invadopodia rather than disorganized actin-cytoskeleton assembly sites. Their identification is based on the occurrence of common invadopodia markers as well as functional invadopodia activity characterized by an increased local proteolytic activity of the extracellular matrix proteins. We demonstrate that CLCA/B deletion impacts the intracellular trafficking and recovery of the matrix metalloproteinase 14 (MMP14) leading to its accumulation at the plasma membrane and induction of invadopodia formation. Importantly, we show that invadopodia formation can be prevented by depletion of MMP14. As such, we propose that CLCA/B regulate invadopodia formation by regulating MMP14 delivery to the plasma membrane.

scholarly journals A DNA-sensing–independent role of a nuclear RNA helicase, DHX9, in stimulation of NF-κB–mediated innate immunity against DNA virus infection

2018 ◽  
Vol 46 (17) ◽  
pp. 9011-9026 ◽  
Author(s):  
Yee Ching Ng ◽  
Woo-Chang Chung ◽  
Hye-Ri Kang ◽  
Hye-Jeong Cho ◽  
Eun-Byeol Park ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Virus Infection ◽  
Rna Helicase ◽  
Dna Sensing ◽  
Dna Virus ◽  
Nuclear Rna ◽  
Stimulation Of

scholarly journals Role of DCP1-DCP2 complex regulated by viral and host microRNAs in DNA virus infection

2018 ◽  
Author(s):  
Yuechao Sun ◽  
Xiaobo Zhang
Keyword(s):  
Virus Infection ◽  
White Spot Syndrome Virus ◽  
Antiviral Immunity ◽  
Underlying Mechanism ◽  
Rnai Pathway ◽  
Dna Virus ◽  
Positive Role ◽  
Host Interactions ◽  
Negative Effect

AbstractThe DCP1-DCP2 complex can regulate the animal antiviral immunity by the decapping of retrovirus RNAs and the suppression of RNAi pathway. However, the influence of DCP1-DCP2 complex on DNA virus infection and the regulation of DCP1-DCP2 complex by microRNAs (miRNAs) remain unclear. In this study, we investigated the role of miRNA-regulated DCP1-DCP2 complex in DNA virus infection. Our results suggested that the DCP1-DCP2 complex played a positive role in the infection of white spot syndrome virus (WSSV), a DNA virus of shrimp. The N-terminal regulatory domain of DCP2 was interacted with the EVH1 domain of DCP1, forming the DCP1-DCP2 complex. Furthermore, a host shrimp miRNA (miR-87) inhibited WSSV infection by targeting the host DCP2 gene and a viral miRNA (WSSV-miR-N46) took a negative effect on WSSV replication by targeting the host DCP1 gene. Therefore, our study provided novel insights into the underlying mechanism of DCP1-DCP2 complex and its regulation by miRNAs in virus-host interactions.The DCP1-DCP2 complex can regulate the animal antiviral immunity by the decapping of retrovirus RNAs and the suppression of RNAi pathway. In the present study, the findings indicated that the silencing of the DCP1-DCP2 complex inhibited the infection of WSSV, a DNA virus of shrimp, suggesting that the DCP1-DCP2 complex facilitated DNA virus infection. Due to the suppressive role of the DCP1-DCP2 complex in RNAi pathway against virus infection, the DCP1-DCP2 complex could promote WSSV infection in shrimp. In this context, our study contributed a novel aspect of the DCP1-DCP2 complex in virus-host interactions. Our study revealed that the host and viral miRNAs could regulate the DCP1-DCP2 complex to affect virus infection. Therefore, our study provided novel insights into the miRNA-mediated regulation of DCP1-DCP2 complex took great effects on RNAi immunity of invertebrates against virus infection.

scholarly journals Know Thyself: RIG-I-Like Receptor Sensing of DNA Virus Infection

2019 ◽  
Vol 93 (23) ◽  
Author(s):  
Yang Zhao ◽  
John Karijolich
Keyword(s):  
Virus Infection ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Rna Virus ◽  
Intrinsic Immunity ◽  
Dna Virus ◽  
Double Stranded Rna ◽  
Recent Advances

ABSTRACT The RIG-I-like receptors (RLRs) are double-stranded RNA-binding proteins that play a role in initiating and modulating cell intrinsic immunity through the recognition of RNA features typically absent from the host transcriptome. While they are initially characterized in the context of RNA virus infection, evidence has now accumulated establishing the role of RLRs in DNA virus infection. Here, we review recent advances in the RLR-mediated restriction of DNA virus infection with an emphasis on the RLR ligands sensed.

A Complete Absence of Missense Mutation in Myosin Regulatory and Essential Light Chain Genes of South Indian Hypertrophic and Dilated Cardiomyopathies

Cardiology ◽  
2018 ◽  
Vol 141 (3) ◽  
pp. 156-166
Author(s):  
Deepa Selvi Rani ◽  
Pratibha Nallari ◽  
Jhansi Rani ◽  
Sheikh Nizamuddin ◽  
Thulasamma Seelamneni ◽  
...  
Keyword(s):  
South India ◽  
Myosin Head ◽  
Light Chains ◽  
Healthy Controls ◽  
Missense Mutations ◽  
Regulatory Light Chains ◽  
Heavy Chains ◽  
Essential Light Chain ◽  
South Indian ◽  
First Time

Background: Myosin is a hexameric contractile protein composed of 2 heavy chains associated with 4 light chains of 2 distinct classes – 2 regulatory light chains (MYL2) and 2 essential light chains (MYL3). The myosin light chains stabilize the long alpha helical neck of the myosin head and regulate the myosin ATPase activities. Objectives: Mutations in MYL2 and MYL3 are reported to be associated with cardiomyopathies. However, there is no study available on these genes in Indian cardiomyopathies, and therefore we planned to study them. Method: For the first time we sequenced MYL2 and MYL3 genes in a total of 248 clinically well-characterized cardiomyopathies consisting of 101 hypertrophic and 147 dilated cases along with 207 healthy controls from south India. Results: Our study revealed a total of 10 variations – 7 in MYL2 and 3 in MYL3, of which 3 are novel variations observed exclusively in cases. However, the 15 causative missense mutations previously reported are totally absent in our study, which showed that the sequences of MYL2 and MYL3 are highly conserved in Indian cases/controls. Conclusions: MYL2 and MYL3 mutations are rare and the least cause of cardiomyopathies in Indians.

scholarly journals p38 inhibition provides anti–DNA virus immunity by regulation of USP21 phosphorylation and STING activation

2017 ◽  
Vol 214 (4) ◽  
pp. 991-1010 ◽  
Author(s):  
Yunfei Chen ◽  
Lufan Wang ◽  
Jiali Jin ◽  
Yi Luan ◽  
Cong Chen ◽  
...  
Keyword(s):  
Virus Infection ◽  
Critical Role ◽  
Adaptor Protein ◽  
Type I Interferons ◽  
Type I ◽  
Innate Immune Responses ◽  
Dna Virus ◽  
Important Pathway ◽  
Hsv 1

Stimulator of IFN genes (STING) is a central adaptor protein that mediates the innate immune responses to DNA virus infection. Although ubiquitination is essential for STING function, how the ubiquitination/deubiquitination system is regulated by virus infection to control STING activity remains unknown. In this study, we found that USP21 is an important deubiquitinating enzyme for STING and that it negatively regulates the DNA virus–induced production of type I interferons by hydrolyzing K27/63-linked polyubiquitin chain on STING. HSV-1 infection recruited USP21 to STING at late stage by p38-mediated phosphorylation of USP21 at Ser538. Inhibition of p38 MAPK enhanced the production of IFNs in response to virus infection and protected mice from lethal HSV-1 infection. Thus, our study reveals a critical role of p38-mediated USP21 phosphorylation in regulating STING-mediated antiviral functions and identifies p38-USP21 axis as an important pathway that DNA virus adopts to avoid innate immunity responses.

Role of galactosylation in the renal pathogenicity of murine immunoglobulin G3 monoclonal cryoglobulins

Blood ◽  
2001 ◽  
Vol 97 (11) ◽  
pp. 3537-3543 ◽  
Author(s):  
Tsuguo Mizuochi ◽  
Yves Pastore ◽  
Kohdoh Shikata ◽  
Aki Kuroki ◽  
Shuichi Kikuchi ◽  
...  
Keyword(s):  
Gel Filtration ◽  
Amino Acid Sequences ◽  
Light Chains ◽  
Remarkable Difference ◽  
Pathogenic Potential ◽  
Myeloma Cells ◽  
Heavy Chains ◽  
Direct Demonstration ◽  
Direct Localization

Cryoglobulin activity associated with murine immunoglobulin G3 (IgG3) has been shown to play a significant role in the development of murine lupuslike glomerulonephritis. A fraction, but not all, IgG3 monoclonal antibodies are capable of inducing a severe acute lupuslike glomerulonephritis as a result of direct localization of IgG3 cryoglobulins, suggesting the importance of qualitative features of cryoglobulins in their nephritogenic activities. Here a remarkable difference is shown in the renal pathogenicity of 2 murine IgG3 monoclonal cryoglobulins, identical in the amino acid sequences of their heavy and light chains but different in galactosylation patterns of oligosaccharide side chains because of their synthesis in different myeloma cells. The antibody lacking the capacity to induce severe glomerulonephritis displayed an increased proportion of galactosylated heavy chains. Changes in conformation, as revealed by gel filtration analysis, reduced cryoglobulin activity, and accelerated clearance could account for the lack of the renal pathogenicity of the more galactosylated variant. This observation provides a direct demonstration for the role of IgG galactosylation in the pathogenic potential of cryoglobulins.

scholarly journals Idiotypes of inulin-binding myeloma proteins localized to variable region light and heavy chains: genetic significance.

1977 ◽  
Vol 146 (5) ◽  
pp. 1294-1304 ◽  
Author(s):  
R Lieberman ◽  
M Vrana ◽  
W Humphrey ◽  
C C Chien ◽  
M Potter
Keyword(s):  
Variable Region ◽  
Light Chains ◽  
Heavy Chains ◽  
Myeloma Proteins ◽  
Genetic Significance

Idiotypes of inulin-binding myeloma proteins (InuBMP) were determined primarly by variable region light chains (VL) or by variable region heavy chains (VH) but needed both chains to be expressed. Recombinant molecules were used to show that individual idiotypes (IdI) of U61, E109, T957, and A4 InuBMP and cross-specific idiotypes (IdXB) of U61 were primarily determined by VL while cross-specific idiotype (IdXA) of A4 was determined mainly by VH. The assignment of genes controlling idiotypes to VH based on allotype linkage (e.g., IdXB) is dubious until the role of the L chain in determining that idiotype is assessed. IdXB has been shown to be a VL-VH marker which presumably is controlled by two unlinked genes. However IdXB can be used as a L chain marker in combinations of strains differing in their L chain genes but having the same permissive H chain genes. Conversely IdXB can be used as a H chain marker in strains having the same permissive L chain genes but differing in their H chain genes.

scholarly journals Clathrin Light Chains: Not to Be Taken so Lightly

2021 ◽  
Vol 9 ◽  
Author(s):  
Jyoti Das ◽  
Mahak Tiwari ◽  
Deepa Subramanyam
Keyword(s):  
Membrane Trafficking ◽  
Coated Vesicle ◽  
Light Chains ◽  
Biological Processes ◽  
Organelle Biogenesis ◽  
Heavy Chains ◽  
Chromosomal Segregation ◽  
Physiological Processes ◽  
Wide Range

Clathrin is a cytosolic protein involved in the intracellular trafficking of a wide range of cargo. It is composed of three heavy chains and three light chains that together form a triskelion, the subunit that polymerizes to form a clathrin coated vesicle. In addition to its role in membrane trafficking, clathrin is also involved in various cellular and biological processes such as chromosomal segregation during mitosis and organelle biogenesis. Although the role of the heavy chains in regulating important physiological processes has been well documented, we still lack a complete understanding of how clathrin light chains regulate membrane traffic and cell signaling. This review highlights the importance and contributions of clathrin light chains in regulating clathrin assembly, vesicle formation, endocytosis of selective receptors and physiological and developmental processes.

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