Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bracovirus-mediated innexin hemichannel closure in cell disassembly.

ABSTRACT: Cell-cell communication is necessary for cellular immune response. Hemichannel closure disrupts communication between intracellular and extracellular environments during polydnavirus-induced immunosuppression in invertebrates. However, the effects of hemichannel closure on cellular immune response are unclear. Here, we examined apoptotic body formation triggered by hemichannel closure in hemocytes of Spodoptera litura infected with bracovirus from the parasitic wasp, Microplitis bicoloratus. We showed that Microplitis bicoloratus bracovirus (MbBV) induced apoptotic cell disassembly, accompanied by hemichannel closure. Hemocyte apoptotic body formation was caused by the dysregulation of the innexins (Inxs), Inx1, Inx2, Inx3, and Inx4, during the MbBV-mediated inhibition of pI3K/AKT signaling and activation of caspase-3, which cleaved gap junction Inx proteins. Our results showed that hemichannel opening or closure in response to various stimuli, which induces the modulation of Inx levels, could inhibit or activate apoptotic body formation, respectively. Therefore, the "hemichannel open and close" model may regulate the cellular immune response.

SUBMITTER: Chen CX

PROVIDER: S-EPMC8008186 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Innexin hemichannel activation by <i>Microplitis bicoloratus</i> ecSOD monopolymer reduces ROS.

Project description:The extracellular superoxide dismutases (ecSODs) secreted by Microplitis bicoloratus reduce the reactive oxygen species (ROS) stimulated by the Microplitis bicoloratus bracovirus. Here, we demonstrate that the bacterial transferase hexapeptide (hexapep) motif and bacterial-immunoglobulin-like (BIg-like) domain of ecSODs bind to the cell membrane and transiently open hemichannels, facilitating ROS reductions. RNAi-mediated ecSOD silencing in vivo elevated ROS in host hemocytes, impairing parasitoid larva development. In vitro, the ecSOD-monopolymer needed to be membrane bound to open hemichannels. Furthermore, the hexapep motif in the beta-sandwich of ecSOD49 and ecSOD58, and BIg-like domain in the signal peptides of ecSOD67 were required for cell membrane binding. Hexapep motif and BIg-like domain deletions induced ecSODs loss of adhesion and ROS reduction failure. The hexapep motif and BIg-like domain mediated ecSOD binding via upregulating innexins and stabilizing the opened hemichannels. Our findings reveal a mechanism through which ecSOD reduces ROS, which may aid in developing anti-redox therapy.

| S-EPMC10993139 | biostudies-literature

Cryo-EM structure of an undocked innexin-6 hemichannel in phospholipids

Project description: Not available

| EMPIAR-10289 | biostudies-other

Cryo-EM structure of an undocked innexin-6 hemichannel in detergent

Project description: Not available

| EMPIAR-10290 | biostudies-other

Connexin43 hemichannel-mediated regulation of connexin43.

Project description:BackgroundMany signaling molecules and pathways that regulate gap junctions (GJs) protein expression and function are, in fact, also controlled by GJs. We, therefore, speculated an existence of the GJ channel-mediated self-regulation of GJs. Using a cell culture model in which nonjunctional connexin43 (Cx43) hemichannels were activated by cadmium (Cd(2+)), we tested this hypothesis.Principal findingsIncubation of Cx43-transfected LLC-PK1 cells with Cd(2+) led to an increased expression of Cx43. This effect of Cd(2+) was tightly associated with JNK activation. Inhibition of JNK abolished the elevation of Cx43. Further analysis revealed that the changes of JNK and Cx43 were controlled by GSH. Supplement of a membrane-permeable GSH analogue GSH ethyl ester or GSH precursor N-acetyl-cystein abrogated the effects of Cd(2+) on JNK activation and Cx43 expression. Indeed, Cd(2+) induced extracellular release of GSH. Blockade of Cx43 hemichannels with heptanol or Cx43 mimetic peptide Gap26 to prevent the efflux of GSH significantly attenuated the Cx43-elevating effects of Cd(2+).ConclusionsCollectively, our results thus indicate that Cd(2+)-induced upregulation of Cx43 is through activation of nonjunctional Cx43 hemichannels. Our findings thus support the existence of a hemichannel-mediated self-regulation of Cx43 and provide novel insights into the molecular mechanisms of Cx43 expression and function.

| S-EPMC3584027 | biostudies-literature

Innexin 3, a new gene required for dorsal closure in Drosophila embryo.

Project description:BACKGROUND: Dorsal closure is a morphogenetic event that occurs during mid-embryogenesis in many insects including Drosophila, during which the ectoderm migrates on the extraembryonic amnioserosa to seal the embryo dorsally. The contribution of the ectoderm in this event has been known for a long time. However, amnioserosa tension and contractibility have recently been shown also to be instrumental to the closure. A critical pre-requisite for dorsal closure is integrity of these tissues that in part is mediated by cell-cell junctions and cell adhesion. In this regard, mutations impairing junction formation and/or adhesion lead to dorsal closure. However, no role for the gap junction proteins Innexins has so far been described. RESULTS AND DISCUSSION: Here, we show that Innexin 1, 2 and 3, are present in the ectoderm but also in the amnioserosa in plaques consistent with gap junctions. However, only the loss of Inx3 leads to dorsal closure defects that are completely rescued by overexpression of inx3::GFP in the whole embryo. Loss of Inx3 leads to the destabilisation of Inx1, Inx2 and DE-cadherin at the plasma membrane, suggesting that these four proteins form a complex. Accordingly, in addition to the known interaction of Inx2 with DE-cadherin, we show that Inx3 can bind to DE-cadherin. Furthermore, Inx3-GFP overexpression recruits DE-cadherin from its wildtype plasma membrane domain to typical Innexin plaques, strengthening the notion that they form a complex. Finally, we show that Inx3 stability is directly dependent on tissue tension. Taken together, we propose that Inx3 is a critical factor for dorsal closure and that it mediates the stability of Inx1, 2 and DE-cadherin by forming a complex.

| S-EPMC3722180 | biostudies-other

Bracovirus Sneaks Into Apoptotic Bodies Transmitting Immunosuppressive Signaling Driven by Integration-Mediated eIF5A Hypusination.

Project description:A typical characteristics of polydnavirus (PDV) infection is a persistent immunosuppression, governed by the viral integration and expression of virulence genes. Recently, activation of caspase-3 by Microplitis bicoloratus bracovirus (MbBV) to cleave Innexins, gap junction proteins, has been highlighted, further promoting apoptotic cell disassembly and apoptotic body (AB) formation. However, whether ABs play a role in immune suppression remains to be determined. Herein, we show that ABs transmitted immunosuppressive signaling, causing recipient cells to undergo apoptosis and dismigration. Furthermore, the insertion of viral-host integrated motif sites damaged the host genome, stimulating eIF5A nucleocytoplasmic transport and activating the eIF5A-hypusination translation pathway. This pathway specifically translates apoptosis-related host proteins, such as P53, CypA, CypD, and CypJ, to drive cellular apoptosis owing to broken dsDNA. Furthermore, translated viral proteins, such Vank86, 92, and 101, known to complex with transcription factor Dip3, positively regulated DHYS and DOHH transcription maintaining the activation of the eIF5A-hypusination. Mechanistically, MbBV-mediated extracellular vesicles contained inserted viral fragments that re-integrated into recipients, potentially via the homologous recombinant repair system. Meanwhile, this stimulation regulated activated caspase-3 levels via PI3K/AKT 308 and 473 dephosphorylation to promote apoptosis of granulocyte-like recipients Sf9 cell; maintaining PI3K/AKT 473 phosphorylation and 308 dephosphorylation inhibited caspase-3 activation leading to dismigration of plasmatocyte-like recipient High Five cells. Together, our results suggest that integration-mediated eIF5A hypusination drives extracellular vesicles for continuous immunosuppression.

| S-EPMC9156803 | biostudies-literature

Organized Disassembly of Photosynthesis During Programmed Cell Death Mediated By Long Chain Bases.

Project description:In plants, pathogen triggered programmed cell death (PCD) is frequently mediated by polar lipid molecules referred as long chain bases (LCBs) or ceramides. PCD interceded by LCBs is a well-organized process where several cell organelles play important roles. In fact, light-dependent reactions in the chloroplast have been proposed as major players during PCD, however, the functional aspects of the chloroplast during PCD are largely unknown. For this reason, we investigated events that lead to disassembly of the chloroplast during PCD mediated by LCBs. To do so, LCB elevation was induced with Pseudomonas syringae pv. tomato (a non-host pathogen) or Fumonisin B1 in Phaseolus vulgaris. Then, we performed biochemical tests to detect PCD triggering events (phytosphingosine rises, MPK activation and H2O2 generation) followed by chloroplast structural and functional tests. Observations of the chloroplast, via optical phenotyping methods combined with microscopy, indicated that the loss of photosynthetic linear electron transport coincides with the organized ultrastructure disassembly. In addition, structural changes occurred in parallel with accumulation of H2O2 inside the chloroplast. These features revealed the collapse of chloroplast integrity and function as a mechanism leading to the irreversible execution of the PCD promoted by LCBs.

| S-EPMC7316715 | biostudies-literature

The Rac activator STEF (Tiam2) regulates cell migration by microtubule-mediated focal adhesion disassembly.

Project description:Focal adhesion (FA) disassembly required for optimal cell migration is mediated by microtubules (MTs); targeting of FAs by MTs coincides with their disassembly. Regrowth of MTs, induced by removal of the MT destabilizer nocodazole, activates the Rho-like GTPase Rac, concomitant with FA disassembly. Here, we show that the Rac guanine nucleotide exchange factor (GEF) Sif and Tiam1-like exchange factor (STEF) is responsible for Rac activation during MT regrowth. Importantly, STEF is required for multiple targeting of FAs by MTs. As a result, FAs in STEF-knockdown cells have a reduced disassembly rate and are consequently enlarged. This leads to reduced speed of migration. Together, these findings suggest a new role for STEF in FA disassembly and cell migration through MT-mediated mechanisms.

| S-EPMC2854589 | biostudies-literature

Gap junctional hemichannel-mediated ATP release and hearing controls in the inner ear.

Project description:Connexin gap junctions play an important role in hearing function, but the mechanism by which this contribution occurs is unknown. Connexins in the cochlea are expressed only in supporting cells; no connexin expression occurs in auditory sensory hair cells. A gap junctional channel is formed by two hemichannels. Here, we show that connexin hemichannels in the cochlea can release ATP at levels that account for the submicromolar concentrations measured in the cochlear fluids in vivo. The release could be increased 3- to 5-fold by a reduction of extracellular Ca2+ or an increase in membrane stress, and blocked by gap junctional blockers. We also demonstrated that extracellular ATP at submicromolar levels apparently affected outer hair cell (OHC) electromotility, which is an active cochlear amplifier determining cochlear sensitivity to sound stimulation in mammals. ATP reduced OHC electromotility and the slope factor of the voltage dependence and shifted the operating point to reduce the active amplifier gain. ATP also reduced the generation of distortion products. Immunofluorescent staining showed that purinergic receptors P2x2 and P2x7 were distributed on the OHC surface. Blockage of P2 receptors eliminated the effect of ATP on the OHC electromotility. The data revealed that there is a hemichannel-mediated, purinergic intercellular signaling pathway between supporting cells and hair cells in the cochlea to control hearing sensitivity. The data also demonstrated a potential source of ATP in the cochlea.

| S-EPMC1317927 | biostudies-literature

AIP1-mediated actin disassembly is required for postnatal germ cell migration and spermatogonial stem cell niche establishment.

Project description:In mammals, spermatogonial stem cells (SSCs) arise from early germ cells called gonocytes, which are derived from primordial germ cells during embryogenesis and remain quiescent until birth. After birth, these germ cells migrate from the center of testicular cord, through Sertoli cells, and toward the basement membrane to form the SSC pool and establish the SSC niche architecture. However, molecular mechanisms underlying germ cell migration and niche establishment are largely unknown. Here, we show that the actin disassembly factor actin interacting protein 1 (AIP1) is required in both germ cells and Sertoli cells to regulate this process. Germ cell-specific or Sertoli cell-specific deletion of Aip1 gene each led to significant defects in germ cell migration after postnatal day 4 or 5, accompanied by elevated levels of actin filaments (F-actin) in the affected cells. Furthermore, our data demonstrated that interaction between germ cells and Sertoli cells, likely through E-cadherin-mediated cell adhesion, is critical for germ cells' migration toward the basement membrane. At last, Aip1 deletion in Sertoli cells decreased SSC self-renewal, increased spermatogonial differentiation, but did not affect the expression and secretion levels of growth factors, suggesting that the disruption of SSC function results from architectural changes in the postnatal niche.

| S-EPMC4650729 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data