Product References
ELFN2 is a postsynaptic cell adhesion molecule with essential roles in controlling group III mGluRs in the brain and neuropsychiatric behavior.
Molecular psychiatry
Dunn HA,Zucca S,Dao M,Orlandi C,Martemyanov KA
The functional characterization of the GPCR interactome has predominantly focused on intracellular binding partners; however, the recent emergence of transsynaptic GPCR complexes represents an additional dimension to GPCR function that has previously been unaccounted for in drug discovery. Here, we characterize ELFN2 as a novel postsynaptic adhesion molecule with a distinct expression pattern throughout the brain and a selective binding with group III metabotropic glutamate receptors (mGluRs) in
Sun Dec 01 00:00:00 EST 2019
Domain-specific expression of meristematic genes is defined by the LITTLE ZIPPER protein DTM in tomato.
Communications biology
Xu Q,Li R,Weng L,Sun Y,Li M,Xiao H
Shoot meristems which harbor a small population of stem cells are responsible for generating new above-ground organs in plants. The proliferation and differentiation of these stem cells is regulated by a genetic pathway involving two key meristematic genes: () and (). However it is not well understood how and expression domains in the shoot meristems are specified and maintained during post-embryogenic development. Here we show that a tomato mutant with fasciated stems flowers and fruits due
Fri Apr 17 00:00:00 EDT 2020
Typhoid toxin exhausts the RPA response to DNA replication stress driving senescence and Salmonella infection.
Nature communications
Ibler AEM,ElGhazaly M,Naylor KL,Bulgakova NA,F El-Khamisy S,Humphreys D
Salmonella Typhi activates the host DNA damage response through the typhoid toxin, facilitating typhoid symptoms and chronic infections. Here we reveal a non-canonical DNA damage response, which we call RING (response induced by a genotoxin), characterized by accumulation of phosphorylated histone H2AX (γH2AX) at the nuclear periphery. RING is the result of persistent DNA damage mediated by toxin nuclease activity and is characterized by hyperphosphorylation of RPA, a sensor of single-stra
Fri Sep 06 00:00:00 EDT 2019
Cyclophilin J limits inflammation through the blockage of ubiquitin chain sensing.
Nature communications
Sheng C,Yao C,Wang Z,Chen H,Zhao Y,Xu D,Huang H,Huang W,Chen S
Maintaining innate immune homeostasis is important for individual health. Npl4 zinc finger (NZF) domain-mediated ubiquitin chain sensing is reported to function in the nuclear factor-kappa B (NF-κB) signal pathway, but the regulatory mechanism remains elusive. Here we show that cyclophilin J (CYPJ), a member of the peptidylprolyl isomerase family, is induced by inflammation. CYPJ interacts with the NZF domain of transform growth factor-β activated kinase 1 binding protein 2 and 3 as w
Mon Oct 22 00:00:00 EDT 2018
Transsynaptic Binding of Orphan Receptor GPR179 to Dystroglycan-Pikachurin Complex Is Essential for the Synaptic Organization of Photoreceptors.
Cell reports
Orlandi C,Omori Y,Wang Y,Cao Y,Ueno A,Roux MJ,Condomitti G,de Wit J,Kanagawa M,Furukawa T,Martemyanov KA
Tue Oct 02 00:00:00 EDT 2018
The Auxiliary Calcium Channel Subunit α2δ4 Is Required for Axonal Elaboration, Synaptic Transmission, and Wiring of Rod Photoreceptors.
Neuron
Wang Y,Fehlhaber KE,Sarria I,Cao Y,Ingram NT,Guerrero-Given D,Throesch B,Baldwin K,Kamasawa N,Ohtsuka T,Sampath AP,Martemyanov KA
Neural circuit wiring relies on selective synapse formation whereby a presynaptic release apparatus is matched with its cognate postsynaptic machinery. At metabotropic synapses, the molecular mechanisms underlying this process are poorly understood. In the mammalian retina, rod photoreceptors form selective contacts with rod ON-bipolar cells by aligning the presynaptic voltage-gated Ca2+ channel directing glutamate release (CaV1.4) with postsynaptic mGluR6 receptors. We show this coordination re
Wed Mar 22 00:00:00 EDT 2017
O-GlcNAcylation is required for B cell homeostasis and antibody responses.
Nature communications
Wu JL,Chiang MF,Hsu PH,Tsai DY,Hung KH,Wang YH,Angata T,Lin KI
O-linked N-acetylglucosamine (O-GlcNAc) transferase (Ogt) catalyzes O-GlcNAc modification. O-GlcNAcylation is increased after cross-linking of the B-cell receptor (BCR), but the physiological function of this reaction is unknown. Here we show that lack of Ogt in B-cell development not only causes severe defects in the activation of BCR signaling, but also perturbs B-cell homeostasis by enhancing apoptosis of mature B cells, partly as a result of impaired response to B-cell activating factor. O-G
Thu Nov 30 00:00:00 EST 2017
SOCS3 Drives Proteasomal Degradation of TBK1 and Negatively Regulates Antiviral Innate Immunity.
Molecular and cellular biology
Liu D,Sheng C,Gao S,Yao C,Li J,Jiang W,Chen H,Wu J,Pan C,Chen S,Huang W
TANK-binding kinase 1 (TBK1)-mediated induction of type I interferon (IFN) plays a critical role in host antiviral responses and immune homeostasis. The negative regulation of TBK1 activity is largely unknown. We report that suppressor of cytokine signaling 3 (SOCS3) inhibits the IFN-β signaling pathway by promoting proteasomal degradation of TBK1. Overexpression and knockdown experiments indicated that SOCS3 is a negative regulator of IFN regulatory factor 3 (IRF3) phosphorylation and IFN-
Wed Jul 01 00:00:00 EDT 2015
eEF1Bγ is a positive regulator of NF-кB signaling pathway.
Biochemical and biophysical research communications
Liu D,Sheng C,Gao S,Jiang W,Li J,Yao C,Chen H,Wu J,Chen S,Huang W
Mitochondrial antiviral-signaling protein (MAVS), as a critical adaptor of RIG-I signaling, bridges viral RNA recognition and downstream signal activation. However, the regulating mechanisms of MAVS are not well understood. In this study, we demonstrated that eukaryotic elongation factor 1B gamma (eEF1Bγ) activates NF-κB signaling pathway through targeting MAVS. GST-pull down and mass spectrometric analysis suggested that eEF1Bγ binds to the CARD domain of MAVS. The interaction
Fri Apr 04 00:00:00 EDT 2014
Sperm-specific AKAP3 is a dual-specificity anchoring protein that interacts with both protein kinase a regulatory subunits via conserved N-terminal amphipathic peptides.
Molecular reproduction and development
Xu K,Qi H
cAMP-dependent PKA (protein kinase A) plays important regulatory roles during mouse spermatogenesis. PKA-mediated signaling has been shown to regulate gene expression, chromatin condensation, capacitation, and motility during sperm development and function, although how PKA is regulated in spatiotemporal manners during spermatogenesis is not fully understood. In the present study, we found that PKA subunit isoforms are expressed and localized differently in meiotic and post-meiotic mouse spermat
Tue Jul 01 00:00:00 EDT 2014
Enhancer of zeste homolog 2 is a negative regulator of mitochondria-mediated innate immune responses.
Journal of immunology (Baltimore, Md. : 1950)
Chen S,Sheng C,Liu D,Yao C,Gao S,Song L,Jiang W,Li J,Huang W
The intracellular RIG-I-like receptors recognize 5′-triphosphate viral genomic RNA and initiate the production of cytokines through mitochondria adaptor VISA. The regulation of this signal pathway is largely unknown. In this study, we report that the histone methyltransferase enhancer of zeste homolog 2 (EZH2) inhibits RIG-I signal pathway in an methyltransferase-independent manner. Knockdown EZH2 expression enhances VISA-induced activation of IFN-β promoter and NF-κB signaling.
Sun Sep 01 00:00:00 EDT 2013
Orphan receptor GPR179 forms macromolecular complexes with components of metabotropic signaling cascade in retina ON-bipolar neurons.
Investigative ophthalmology & visual science
Orlandi C,Cao Y,Martemyanov KA
In the mammalian retina, synaptic transmission between light-excited rod photoreceptors and downstream ON-bipolar neurons is indispensable for dim vision, and disruption of this process leads to congenital stationary night blindness in human patients. The ON-bipolar neurons use the metabotropic signaling cascade, initiated by the mGluR6 receptor, to generate depolarizing responses to light-induced changes in neurotransmitter glutamate release from the photoreceptor axonal terminals. Evidence for
Tue Oct 29 00:00:00 EDT 2013
The p16-specific reactivation and inhibition of cell migration through demethylation of CpG islands by engineered transcription factors.
Human gene therapy
Zhang B,Xiang S,Zhong Q,Yin Y,Gu L,Deng D
Methylation of CpG islands inactivates transcription of tumor suppressor genes including p16 (CDKN2A). Inhibitors of DNA methylation and histone deacylation are recognized as useful cancer therapeutic chemicals through reactivation of the expression of methylated genes. However, these inhibitors are not target gene-specific, so that they lead to serious side effects as regular cytotoxic chemotherapy agents. To explore the feasibility of methylated gene-specific reactivation by artificial transcr
Mon Oct 01 00:00:00 EDT 2012
CCAAT/enhancer binding protein beta2 is involved in growth hormone-regulated insulin-like growth factor-II gene expression in the liver of rainbow trout (Oncorhynchus mykiss).
Endocrinology
Lo JH,Chen TT
Previously, we showed that levels of different CCAAT/enhancer binding protein (C/EBP) mRNAs in the liver of rainbow trout were modulated by GH and suggested that C/EBPs might be involved in GH-induced IGF-II gene expression. As a step toward further investigation, we have developed monospecific polyclonal antibodies to detect rainbow trout C/EBPalpha, -beta1, -beta2, and -delta2 isoform proteins. Injection of GH into adult rainbow trout resulted in a significant increase of C/EBPbeta1, C/EBPbeta
Sat May 01 00:00:00 EDT 2010
Activation of swelling-activated chloride current by tumor necrosis factor-alpha requires ClC-3-dependent endosomal reactive oxygen production.
The Journal of biological chemistry
Matsuda JJ,Filali MS,Moreland JG,Miller FJ,Lamb FS
ClC-3 is a Cl-/H+ antiporter required for intra-endosomal reactive oxygen species (ROS) generation by Nox1. ClC-3 current is distinct from the swelling activated chloride current (IClswell), but over-expression of ClC-3 can activate currents that resemble IClswell. Since H2O2 activates IClswell directly, we hypothesized that ClC-3-dependent, endosomal ROS production activates IClswell. Whole-cell perforated patch clamp methods were used to record Cl- currents in cultured aortic vascular smooth m
Fri Jul 23 00:00:00 EDT 2010
TAZ promotes cell proliferation and epithelial-mesenchymal transition and is inhibited by the hippo pathway.
Molecular and cellular biology
Lei QY,Zhang H,Zhao B,Zha ZY,Bai F,Pei XH,Zhao S,Xiong Y,Guan KL
TAZ is a WW domain containing a transcription coactivator that modulates mesenchymal differentiation and development of multiple organs. In this study, we show that TAZ is phosphorylated by the Lats tumor suppressor kinase, a key component of the Hippo pathway, whose alterations result in organ and tissue hypertrophy in Drosophila and contribute to tumorigenesis in humans. Lats phosphorylates TAZ on several serine residues in the conserved HXRXXS motif and creates 14-3-3 binding sites, leading t
Tue Apr 01 00:00:00 EDT 2008
