Abstract:
:l-Glutamate is the main excitatory neurotransmitter in the brain, with postsynaptic responses to its release predominantly mediated by AMPA-type glutamate receptors (AMPARs). A critical component of synaptic plasticity involves changes in the number of responding postsynaptic receptors, which are dynamically recruited to and anchored at postsynaptic sites. Emerging findings continue to shed new light on molecular mechanisms that mediate AMPAR postsynaptic trafficking and localization. Accordingly, unconventional secretory trafficking of AMPARs occurs in dendrites, from the endoplasmic reticulum (ER) through the ER-Golgi intermediary compartment directly to recycling endosomes, independent of the Golgi apparatus. Upon exocytosis, AMPARs diffuse in the plasma membrane to reach the postsynaptic site, where they are trapped to contribute to transmission. This trapping occurs through a combination of both intracellular interactions, such as TARP (transmembrane AMPAR regulatory protein) binding to α-actinin-stabilized PSD-95, and extracellular interactions through the receptor amino-terminal domain. These anchoring mechanisms may facilitate precise receptor positioning with respect to glutamate release sites to enable efficient synaptic transmission.
journal_name
Sci Signaljournal_title
Science signalingauthors
Buonarati OR,Hammes EA,Watson JF,Greger IH,Hell JWdoi
10.1126/scisignal.aar6889subject
Has Abstractpub_date
2019-01-01 00:00:00issue
562eissn
1945-0877issn
1937-9145pii
12/562/eaar6889journal_volume
12pub_type
杂志文章,评审abstract::Genetic diversity in human natural killer (NK) cell receptors is linked to resistance and susceptibility to many diseases. Here, we tested the effect of this diversity on the nanoscale organization of killer cell immunoglobulin-like receptors (KIRs). Using superresolution microscopy, we found that inhibitory KIRs enco...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaw9252
更新日期:2019-12-17 00:00:00
abstract::Activation of vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) by VEGF binding is critical for vascular morphogenesis. In addition, VEGF disrupts the endothelial barrier by triggering the phosphorylation and turnover of the junctional molecule VE-cadherin, a process mediated by the VEGFR2 downstream effec...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aad9256
更新日期:2016-07-19 00:00:00
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
更新日期:2014-05-13 00:00:00
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
更新日期:2011-09-27 00:00:00
abstract::Fragile X syndrome (FXS) mental retardation is caused by loss-of-function mutations in an RNA-binding protein, fragile X mental retardation protein (FMRP). Previous studies in patients or animal models of FXS have identified alterations in dendritic spine structure, as well as synaptic plasticity induced by metabotrop...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/stke.15pe6
更新日期:2008-02-05 00:00:00
abstract::Epithelial cell polarity is linked to the control of tissue growth and tumorigenesis. The tumor suppressor and cell polarity protein lethal-2-giant larvae (Lgl) promotes Hippo signaling and inhibits Notch signaling to restrict tissue growth in Drosophila melanogaster Notch signaling is greater in lgl mutant tissue tha...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aar1976
更新日期:2018-06-05 00:00:00
abstract::The PAR-1-MARK pathway controls cell polarity through the phosphorylation of microtubule-associated proteins. Rho-Rac guanine nucleotide exchange factor 2 (ARHGEF2), which activates Ras homolog family member A (RHOA), is anchored to the microtubule network and sequestered in an inhibited state through binding to dynei...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aan3286
更新日期:2017-10-31 00:00:00
abstract::Under drought stress, abscisic acid (ABA) triggers closure of leaf cell pores called stomata, which are formed by two specialized cells called guard cells in plant epidermis. Two pathways downstream of ABA stimulate phosphorylation of the S-type anion channels SLAC1 (slow anion channel associated 1) and SLAH3 (SLAC1 h...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2005703
更新日期:2014-09-09 00:00:00
abstract::Chimeric antigen receptors (CARs) link an antigen recognition domain to intracellular signaling domains to redirect T cell specificity and function. T cells expressing CARs with CD28/CD3ζ or 4-1BB/CD3ζ signaling domains are effective at treating refractory B cell malignancies but exhibit differences in effector functi...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aat6753
更新日期:2018-08-21 00:00:00
abstract::For the first 30 years since its discovery, reversible protein acetylation has been studied and understood almost exclusively in the context of histone modification and gene transcription. With the discovery of non-histone acetylated proteins and acetylation-modifying enzymes in cellular compartments outside the nucle...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.297pe76
更新日期:2009-11-17 00:00:00
abstract::The role of mucin 1 (MUC1) in protecting epithelia from microbial infection, enzymatic digestion, and other irritants has been appreciated for some time. In addition, MUC1 serves as a barrier to embryo implantation. MUC1 is highly abundant in many tumors in which its role in barrier function may serve to protect cells...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.127pe35
更新日期:2008-07-08 00:00:00
abstract::Mineralocorticoid receptor (MR) antagonists are effective at treating heart failure. In this issue of Science Signaling, Oakley et al. provide new insight into their cardioprotective actions and highlight the importance of the opposing relationship between the MR and the related glucocorticoid receptor (GR) in the res...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.aaw8715
更新日期:2019-04-16 00:00:00
abstract::Educated natural killer (NK) cells have inhibitory receptors specific for self major histocompatibility complex (MHC) class I molecules and kill cancer cells more efficiently than do NK cells that do not have such receptors (hyporesponsive NK cells). The mechanism behind this functional empowerment through education h...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aai9200
更新日期:2018-02-13 00:00:00
abstract::Toll-like receptor (TLR) signaling regulates macrophage activation and effector cytokine propagation in the constrained environment of a tissue. In macrophage populations, TLR4 stimulates the dose-dependent transcription of nuclear factor κB (NF-κB) target genes. However, using single-RNA counting, we found that indiv...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaf3998
更新日期:2018-07-24 00:00:00
abstract::The cytokine interleukin-22 (IL-22), which is a member of the IL-10 family, is produced exclusively by immune cells and activates signal transducer and activator of transcription 3 (STAT3) in nonimmune cells, such as hepatocytes, keratinocytes, and colonic epithelial cells, to drive various processes central to tissue...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aad9887
更新日期:2016-09-27 00:00:00
abstract::Secreted IgD concentration depends on the presence of microbiota. ...
journal_title:Science signaling
pub_type: 评论,杂志文章,评审
doi:10.1126/scisignal.aan0005
更新日期:2017-02-21 00:00:00
abstract::Progression through mitosis depends on a large number of protein complexes that regulate the major structural and physiological changes necessary for faithful chromosome segregation. Most, if not all, of the mitotic processes are regulated by a set of mitotic protein kinases that control protein activity by phosphoryl...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2001993
更新日期:2011-11-08 00:00:00
abstract::Precise control of the activity and abundance of ubiquitin-conjugating enzymes (E2s) ensures fidelity in ubiquitin chain synthesis. In this issue of Science Signaling, Liess et al. demonstrate that the human anaphase-promoting complex (APC/C)-associated E2 UBE2S adopts an autoinhibited dimeric state that increases the...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.abd9892
更新日期:2020-10-20 00:00:00
abstract::The hexosamine biosynthetic pathway, whose end product is UDP-N acetylglucosamine (UDP-GlcNAc), lies at the base of cellular glycosylation pathways, including glycosylation of lipids, formation of heparin sulfated proteoglycans, and N- and O-linked glycosylation of proteins. Forward genetic studies in Drosophila have ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2002789
更新日期:2012-01-17 00:00:00
abstract::The K+/Cl- cotransporter KCC2 is a molecular switch between excitatory and inhibitory effects of GABAergic inputs into neurons. In a pair of exciting studies, Watanabe et al. and Pisella et al. elucidate the role of KCC2 dephosphorylation in this process and reveal its consequences for neurodevelopment and nervous sys...
journal_title:Science signaling
pub_type: 评论,杂志文章,评审
doi:10.1126/scisignal.aay8960
更新日期:2019-10-15 00:00:00
abstract::Chemoattractants induce cell migration through the activation of a distinct family of structurally related heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors. Over the past few years, several receptors in this family have been identified that recognize different classes of chemoattractants...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.259pe10
更新日期:2009-02-24 00:00:00
abstract::Intracellular calcium (Ca2+) signals are of prime importance for cellular function and behavior and are underpinned by a plethora of Ca2+ channels, pumps, transporters, and binding proteins that are regulated in complex ways. A series of biennial meetings, the International Meetings of the European Calcium Society (EC...
journal_title:Science signaling
pub_type:
doi:10.1126/scisignal.aaz0961
更新日期:2019-09-17 00:00:00
abstract::Oxytocin and vasopressin mediate various physiological functions that are important for osmoregulation, reproduction, cardiovascular function, social behavior, memory, and learning through four G protein-coupled receptors that are also implicated in high-profile disorders. Targeting these receptors is challenging beca...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aan3398
更新日期:2017-12-05 00:00:00
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
更新日期:2016-01-05 00:00:00
abstract::Signaling pathways control cell fate decisions that ultimately determine the behavior of cancer cells. Therefore, the dynamics of pathway activity may contain prognostically relevant information different from that contained in the static nature of other types of biomarkers. To investigate this hypothesis, we characte...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aab0990
更新日期:2015-12-22 00:00:00
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
更新日期:2014-09-30 00:00:00
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
更新日期:2016-10-11 00:00:00
abstract::Jasmonates control defense gene expression, growth, and fertility throughout the plant kingdom and have been studied extensively in Arabidopsis thaliana. The prohormone jasmonic acid (JA) is conjugated to amino acids such as isoleucine to form the active hormone jasmonoyl-isoleucine (JA-Ile). A series of breakthroughs...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.3109cm4
更新日期:2010-02-16 00:00:00
abstract::The activation of T cells requires the guanine nucleotide exchange factor VAV1. Using mice in which a tag for affinity purification was attached to endogenous VAV1 molecules, we analyzed by quantitative mass spectrometry the signaling complex that assembles around activated VAV1. Fifty VAV1-binding partners were ident...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aar3083
更新日期:2018-07-10 00:00:00
abstract::The beta-amyloid (Abeta) peptide is associated with the pathogenesis of Alzheimer's disease (AD). Evidence gathered over the last two decades suggests that the gradual accumulation of soluble and insoluble Abeta peptide species triggers a cascade of events that leads to the clinical manifestation of AD. Abeta accumula...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.293re8
更新日期:2009-10-20 00:00:00