Neuroligin-2 as a central organizer of inhibitory synapses in health and disease.

Abstract:

:Postsynaptic organizational protein complexes play central roles both in orchestrating synapse formation and in defining the functional properties of synaptic transmission that together shape the flow of information through neuronal networks. A key component of these organizational protein complexes is the family of synaptic adhesion proteins called neuroligins. Neuroligins form transsynaptic bridges with presynaptic neurexins to regulate various aspects of excitatory and inhibitory synaptic transmission. Neuroligin-2 (NLGN2) is the only member that acts exclusively at GABAergic inhibitory synapses. Altered expression and mutations in NLGN2 and several of its interacting partners are linked to cognitive and psychiatric disorders, including schizophrenia, autism, and anxiety. Research on NLGN2 has fundamentally shaped our understanding of the molecular architecture of inhibitory synapses. Here, we discuss the current knowledge on the molecular and cellular functions of mammalian NLGN2 and its role in the neuronal circuitry that regulates behavior in rodents and humans.

journal_name

Sci Signal

journal_title

Science signaling

authors

Ali H,Marth L,Krueger-Burg D

doi

10.1126/scisignal.abd8379

subject

Has Abstract

pub_date

2020-12-22 00:00:00

issue

663

eissn

1945-0877

issn

1937-9145

pii

13/663/eabd8379

journal_volume

13

pub_type

杂志文章,评审
  • VGF, a new player in antidepressant action?

    abstract::Recent studies have identified adaptations of intracellular signaling pathways and target genes that could contribute or modulate the action of antidepressant drugs, as well as exercise-mediated antidepressant responses. Understanding these adaptations, particularly those changes that are common to diverse antidepress...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/stke.118pe19

    authors: Malberg JE,Monteggia LM

    更新日期:2008-05-06 00:00:00

  • Casein kinase 2 (CK2) phosphorylates the deubiquitylase OTUB1 at Ser16 to trigger its nuclear localization.

    abstract::The deubiquitylating enzyme OTUB1 is present in all tissues and targets many substrates, in both the cytosol and nucleus. We found that casein kinase 2 (CK2) phosphorylated OTUB1 at Ser(16) to promote its nuclear accumulation in cells. Pharmacological inhibition or genetic ablation of CK2 blocked the phosphorylation o...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaa0441

    authors: Herhaus L,Perez-Oliva AB,Cozza G,Gourlay R,Weidlich S,Campbell DG,Pinna LA,Sapkota GP

    更新日期:2015-04-14 00:00:00

  • Transforming growth factor-β and Notch ligands act as opposing environmental cues in regulating the plasticity of type 3 innate lymphoid cells.

    abstract::Group 3 innate lymphoid cells (ILC3s) are composed of subsets that are either positive or negative for the natural cytotoxicity receptor (NCR) NKp46 (encoded by Ncr1). ILC3s are located at mucosal sites, such as in the intestine and lung, where they are exposed to billions of commensal microbes and potentially harmful...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaf2176

    authors: Viant C,Rankin LC,Girard-Madoux MJ,Seillet C,Shi W,Smyth MJ,Bartholin L,Walzer T,Huntington ND,Vivier E,Belz GT

    更新日期:2016-05-03 00:00:00

  • Pressure-induced oxidative activation of PKG enables vasoregulation by Ca2+ sparks and BK channels.

    abstract::Activation of Ca2+-sensitive, large-conductance potassium (BK) channels in vascular smooth muscle cells (VSMCs) by local, ryanodine receptor-mediated Ca2+ signals (Ca2+ sparks) acts as a brake on pressure-induced (myogenic) vasoconstriction-a fundamental mechanism that regulates blood flow in small resistance arteries...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaf6625

    authors: Khavandi K,Baylie RA,Sugden SA,Ahmed M,Csato V,Eaton P,Hill-Eubanks DC,Bonev AD,Nelson MT,Greenstein AS

    更新日期:2016-10-11 00:00:00

  • Phosphorylation of Mad controls competition between wingless and BMP signaling.

    abstract::Bone morphogenetic proteins (BMPs) and Wnts are growth factors that provide essential patterning signals for cell proliferation and differentiation. Here, we describe a molecular mechanism by which the phosphorylation state of the Drosophila transcription factor Mad determines its ability to transduce either BMP or Wi...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2002034

    authors: Eivers E,Demagny H,Choi RH,De Robertis EM

    更新日期:2011-10-11 00:00:00

  • Radiation inhibits salivary gland function by promoting STIM1 cleavage by caspase-3 and loss of SOCE through a TRPM2-dependent pathway.

    abstract::Store-operated Ca2+ entry (SOCE) is critical for salivary gland fluid secretion. We report that radiation treatment caused persistent salivary gland dysfunction by activating a TRPM2-dependent mitochondrial pathway, leading to caspase-3-mediated cleavage of stromal interaction molecule 1 (STIM1) and loss of SOCE. Afte...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aal4064

    authors: Liu X,Gong B,de Souza LB,Ong HL,Subedi KP,Cheng KT,Swaim W,Zheng C,Mori Y,Ambudkar IS

    更新日期:2017-06-06 00:00:00

  • Inhibition of the oncogenic fusion protein EWS-FLI1 causes G2-M cell cycle arrest and enhanced vincristine sensitivity in Ewing's sarcoma.

    abstract::Ewing's sarcoma (ES) is a rare and highly malignant cancer that grows in the bones or surrounding tissues mostly affecting adolescents and young adults. A chimeric fusion between the RNA binding protein EWS and the ETS family transcription factor FLI1 (EWS-FLI1), which is generated from a chromosomal translocation, is...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aam8429

    authors: Zöllner SK,Selvanathan SP,Graham GT,Commins RMT,Hong SH,Moseley E,Parks S,Haladyna JN,Erkizan HV,Dirksen U,Hogarty MD,Üren A,Toretsky JA

    更新日期:2017-10-03 00:00:00

  • T cell receptor signals to NF-κB are transmitted by a cytosolic p62-Bcl10-Malt1-IKK signalosome.

    abstract::Antigen-mediated stimulation of the T cell receptor (TCR) triggers activation of nuclear factor κB (NF-κB), a key transcriptional regulator of T cell proliferation and effector cell differentiation. TCR signaling to NF-κB requires both the Carma1-Bcl10-Malt1 (CBM) complex and the inhibitor of κB (IκB) kinase (IKK) com...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2004882

    authors: Paul S,Traver MK,Kashyap AK,Washington MA,Latoche JR,Schaefer BC

    更新日期:2014-05-13 00:00:00

  • Quantifying crosstalk among interferon-γ, interleukin-12, and tumor necrosis factor signaling pathways within a TH1 cell model.

    abstract::T helper (T(H)) cells integrate biochemical cues present in the tissue microenvironment and produce cytokines that orchestrate immune responses. Previous discoveries have revealed a qualitative understanding of how T(H) cells process this biochemical information; however, the lack of methods to quantify how well these...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2002657

    authors: Klinke DJ 2nd,Cheng N,Chambers E

    更新日期:2012-04-17 00:00:00

  • mTORC1 amplifies the ATF4-dependent de novo serine-glycine pathway to supply glycine during TGF-β1-induced collagen biosynthesis.

    abstract::The differentiation of fibroblasts into a transient population of highly activated, extracellular matrix (ECM)-producing myofibroblasts at sites of tissue injury is critical for normal tissue repair. Excessive myofibroblast accumulation and persistence, often as a result of a failure to undergo apoptosis when tissue r...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aav3048

    authors: Selvarajah B,Azuelos I,Platé M,Guillotin D,Forty EJ,Contento G,Woodcock HV,Redding M,Taylor A,Brunori G,Durrenberger PF,Ronzoni R,Blanchard AD,Mercer PF,Anastasiou D,Chambers RC

    更新日期:2019-05-21 00:00:00

  • Transduction of redox signaling by electrophile-protein reactions.

    abstract::Over the last 50 years, the posttranslational modification (PTM) of proteins has emerged as a central mechanism for cells to regulate metabolism, growth, differentiation, cell-cell interactions, and immune responses. By influencing protein structure and function, PTM leads to a multiplication of proteome diversity. Re...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.290re7

    authors: Rudolph TK,Freeman BA

    更新日期:2009-09-29 00:00:00

  • Tumor suppression by LKB1: SIK-ness prevents metastasis.

    abstract::The LKB1 serine-threonine kinase is a tumor suppressor that is inactivated in a large number of sporadic human lung non-small cell carcinomas (NSCLCs) and cervical cancers. Genetic deletion of LKB1 in various mouse tissues results in tumorigenesis, and loss of LKB1 increases metastasis in a mouse model of NSCLC. LKB1 ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.286pe55

    authors: Shaw RJ

    更新日期:2009-09-01 00:00:00

  • Large-scale discovery of ERK2 substrates identifies ERK-mediated transcriptional regulation by ETV3.

    abstract::The mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 2 (ERK2) is ubiquitously expressed in mammalian tissues and is involved in a wide range of biological processes. Although MAPKs have been intensely studied, identification of their substrates remains challenging. We have optimized a chem...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2002010

    authors: Carlson SM,Chouinard CR,Labadorf A,Lam CJ,Schmelzle K,Fraenkel E,White FM

    更新日期:2011-10-25 00:00:00

  • Parkin mediates mitophagy during beige-to-white fat conversion.

    abstract::In this issue of Science Signaling, Lu et al reveal a role for Parkin-mediated mitophagy in beige-to-white adipocyte transition. In the absence of Parkin, mitochondria in thermogenic beige adipocytes are preserved even after the elimination of cold mimetic stimuli-in contrast to their typical elimination during the wh...

    journal_title:Science signaling

    pub_type: 评论,杂志文章,评审

    doi:10.1126/scisignal.aat1082

    authors: Sarraf SA,Youle RJ

    更新日期:2018-04-24 00:00:00

  • ER stress in pancreatic beta cells: the thin red line between adaptation and failure.

    abstract::Secretory cells, such as pancreatic beta cells, face the challenge of increasing protein synthesis severalfold during acute or chronic stimulation. This poses a burden on the endoplasmic reticulum (ER), the organelle where proinsulin synthesis and folding takes place. Thus, beta cells use various adaptive mechanisms t...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.3110pe7

    authors: Eizirik DL,Cnop M

    更新日期:2010-02-23 00:00:00

  • Emerging from the shade of p53 mutants: N-terminally truncated variants of the p53 family in EMT signaling and cancer progression.

    abstract::The prevailing view has been that N-terminally truncated p53 family isoforms (ΔNp53, ΔNp63, and DNp73) predominantly counteract cell cycle arrest and apoptosis. Recent progress in the field extend these well-known functions and place these isoforms in the center of a comprehensive regulatory network controlling major ...

    journal_title:Science signaling

    pub_type: 杂志文章,评审

    doi:10.1126/scisignal.2005699

    authors: Engelmann D,Pützer BM

    更新日期:2014-09-30 00:00:00

  • Beta-adrenergic regulation of the L-type Ca2+ channel Ca(V)1.2 by PKA rekindles excitement.

    abstract::When we are frightened, our hearts beat more rapidly and forcefully so we can fight more intensely or run away faster. This fight-or-flight response is triggered by the release of norepinephrine from neurons of the sympathetic nervous system. Norepinephrine activates the classic β-adrenergic receptor-heterotrimeric G(...

    journal_title:Science signaling

    pub_type: 评论,杂志文章

    doi:10.1126/scisignal.3141pe33

    authors: Hell JW

    更新日期:2010-09-28 00:00:00

  • Genome to kinome: species-specific peptide arrays for kinome analysis.

    abstract::Tools for conducting high-throughput kinome analysis do not exist for many species. For example, two commonly used techniques for monitoring phosphorylation events are phosphorylation-specific antibodies and peptide arrays. The majority of phosphorylation-specific antibodies are for human or mouse targets, and the con...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.254pl1

    authors: Jalal S,Arsenault R,Potter AA,Babiuk LA,Griebel PJ,Napper S

    更新日期:2009-01-20 00:00:00

  • Receptor cooperation in B cells.

    abstract::TLR4-stimulated B cell activation is mediated by the tyrosine kinase Syk and depends on the B cell receptor. ...

    journal_title:Science signaling

    pub_type: 评论,杂志文章

    doi:10.1126/scisignal.aan7951

    authors: Foley JF

    更新日期:2017-05-23 00:00:00

  • Tyrosine phosphorylation of the Gα-interacting protein GIV promotes activation of phosphoinositide 3-kinase during cell migration.

    abstract::GIV (Gα-interacting vesicle-associated protein; also known as Girdin) enhances Akt activation downstream of multiple growth factor- and G protein (heterotrimeric guanosine 5'-triphosphate-binding protein)-coupled receptors to trigger cell migration and cancer invasion. We demonstrate that GIV is a tyrosine phosphoprot...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2002049

    authors: Lin C,Ear J,Pavlova Y,Mittal Y,Kufareva I,Ghassemian M,Abagyan R,Garcia-Marcos M,Ghosh P

    更新日期:2011-09-27 00:00:00

  • Mechanochemotransduction during cardiomyocyte contraction is mediated by localized nitric oxide signaling.

    abstract::Cardiomyocytes contract against a mechanical load during each heartbeat, and excessive mechanical stress leads to heart diseases. Using a cell-in-gel system that imposes an afterload during cardiomyocyte contraction, we found that nitric oxide synthase (NOS) was involved in transducing mechanical load to alter Ca(2+) ...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2005046

    authors: Jian Z,Han H,Zhang T,Puglisi J,Izu LT,Shaw JA,Onofiok E,Erickson JR,Chen YJ,Horvath B,Shimkunas R,Xiao W,Li Y,Pan T,Chan J,Banyasz T,Tardiff JC,Chiamvimonvat N,Bers DM,Lam KS,Chen-Izu Y

    更新日期:2014-03-18 00:00:00

  • Induction of metabolic quiescence defines the transitional to follicular B cell switch.

    abstract::Transitional B cells must actively undergo selection for self-tolerance before maturing into their resting follicular B cell successors. We found that metabolic quiescence was acquired at the follicular B cell stage in both humans and mice. In follicular B cells, the expression of genes involved in ribosome biogenesis...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaw5573

    authors: Farmer JR,Allard-Chamard H,Sun N,Ahmad M,Bertocchi A,Mahajan VS,Aicher T,Arnold J,Benson MD,Morningstar J,Barmettler S,Yuen G,Murphy SJH,Walter JE,Ghebremichael M,Shalek AK,Batista F,Gerszten R,Pillai S

    更新日期:2019-10-22 00:00:00

  • Quantitative analysis of protein-lipid interactions using tryptophan fluorescence.

    abstract::The fluorescent properties of the amino acid tryptophan make it a useful tool for fluorometric assays. Because tryptophan fluorescence is remarkably sensitive to the polarity of the environment, it can be used to determine the affinity of tryptophan-containing peptides for phospholipid vesicles of varying compositions...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.299pl4

    authors: Kraft CA,Garrido JL,Leiva-Vega L,Romero G

    更新日期:2009-12-01 00:00:00

  • Heterogeneity in human hippocampal CaMKII transcripts reveals allosteric hub-dependent regulation.

    abstract::Calcium/calmodulin-dependent protein kinase II (CaMKII) plays a central role in Ca2+ signaling throughout the body. In the hippocampus, CaMKII is required for learning and memory. Vertebrate genomes encode four CaMKII homologs: CaMKIIα, CaMKIIβ, CaMKIIγ, and CaMKIIδ. All CaMKIIs consist of a kinase domain, a regulator...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaz0240

    authors: Sloutsky R,Dziedzic N,Dunn MJ,Bates RM,Torres-Ocampo AP,Boopathy S,Page B,Weeks JG,Chao LH,Stratton MM

    更新日期:2020-07-21 00:00:00

  • A phosphorylated pseudokinase complex controls cell wall synthesis in mycobacteria.

    abstract::Prokaryotic cell wall biosynthesis is coordinated with cell growth and division, but the mechanisms regulating this dynamic process remain obscure. Here, we describe a phosphorylation-dependent regulatory complex that controls peptidoglycan (PG) biosynthesis in Mycobacterium tuberculosis. We found that PknB, a PG-resp...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2002525

    authors: Gee CL,Papavinasasundaram KG,Blair SR,Baer CE,Falick AM,King DS,Griffin JE,Venghatakrishnan H,Zukauskas A,Wei JR,Dhiman RK,Crick DC,Rubin EJ,Sassetti CM,Alber T

    更新日期:2012-01-24 00:00:00

  • Cycles of ubiquitination and deubiquitination critically regulate growth factor-mediated activation of Akt signaling.

    abstract::K63-linked ubiquitination of Akt is a posttranslational modification that plays a critical role in growth factor-mediated membrane recruitment and activation of Akt. Although E3 ligases involved in growth factor-induced ubiquitination of Akt have been defined, the deubiquitinating enzyme (DUB) that triggers deubiquiti...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2003197

    authors: Yang WL,Jin G,Li CF,Jeong YS,Moten A,Xu D,Feng Z,Chen W,Cai Z,Darnay B,Gu W,Lin HK

    更新日期:2013-01-08 00:00:00

  • Temperature-activated ion channels in neural crest cells confer maternal fever-associated birth defects.

    abstract::Birth defects of the heart and face are common, and most have no known genetic cause, suggesting a role for environmental factors. Maternal fever during the first trimester is an environmental risk factor linked to these defects. Neural crest cells are precursor populations essential to the development of both at-risk...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aal4055

    authors: Hutson MR,Keyte AL,Hernández-Morales M,Gibbs E,Kupchinsky ZA,Argyridis I,Erwin KN,Pegram K,Kneifel M,Rosenberg PB,Matak P,Xie L,Grandl J,Davis EE,Katsanis N,Liu C,Benner EJ

    更新日期:2017-10-10 00:00:00

  • Gain-of-function mutations in protein kinase Cα (PKCα) may promote synaptic defects in Alzheimer's disease.

    abstract::Alzheimer's disease (AD) is a progressive dementia disorder characterized by synaptic degeneration and amyloid-β (Aβ) accumulation in the brain. Through whole-genome sequencing of 1345 individuals from 410 families with late-onset AD (LOAD), we identified three highly penetrant variants in PRKCA, the gene that encodes...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.aaf6209

    authors: Alfonso SI,Callender JA,Hooli B,Antal CE,Mullin K,Sherman MA,Lesné SE,Leitges M,Newton AC,Tanzi RE,Malinow R

    更新日期:2016-05-10 00:00:00

  • 2015: Signaling Breakthroughs of the Year.

    abstract::This year's signaling breakthroughs highlight insights into the pathogenesis or treatment of cancer, malaria, and neurodegenerative disorders; reveal molecular insights into cell death; and identify signals that could be leveraged to prevent plant parasitism or engineer bacteria as microbial fuel cells. ...

    journal_title:Science signaling

    pub_type: 社论

    doi:10.1126/scisignal.aad9795

    authors: Adler EM

    更新日期:2016-01-05 00:00:00

  • STIM2 enhances receptor-stimulated Ca²⁺ signaling by promoting recruitment of STIM1 to the endoplasmic reticulum-plasma membrane junctions.

    abstract::A central component of receptor-evoked Ca(2+) signaling is store-operated Ca(2+) entry (SOCE), which is activated by the assembly of STIM1-Orai1 channels in endoplasmic reticulum (ER) and plasma membrane (PM) (ER-PM) junctions in response to depletion of ER Ca(2+). We report that STIM2 enhances agonist-mediated activa...

    journal_title:Science signaling

    pub_type: 杂志文章

    doi:10.1126/scisignal.2005748

    authors: Ong HL,de Souza LB,Zheng C,Cheng KT,Liu X,Goldsmith CM,Feske S,Ambudkar IS

    更新日期:2015-01-13 00:00:00