Abstract:
:Parkinson's disease (PD) is a neurodegenerative disorder in which the loss of dopaminergic neurons in the midbrain (mDA neurons) causes progressive loss of motor control and function. Using embryonic and mDA neurons, midbrain tissue from mice, and differentiated human neural stem cells, we investigated the mechanisms controlling the survival of mDA neurons. We found that the extracellular matrix protein laminin-511 (LM511) promoted the survival and differentiation of mDA neurons. LM511 bound to integrin α3β1 and activated the transcriptional cofactor YAP. LM511-YAP signaling enhanced cell survival by inducing the expression of the microRNA miR-130a, which suppressed the synthesis of the cell death-associated protein PTEN. In addition, LM511-YAP signaling increased the expression of transcription factors critical for mDA identity, such as LMX1A and PITX3, and prevented the loss of mDA neurons in response to oxidative stress, a finding that warrants further investigation to assess therapeutic potential for PD patients. We propose that by enhancing LM511-YAP signaling, it may be possible to prevent mDA neuron degeneration in PD or enhance the survival of mDA neurons in cell replacement therapies.
journal_name
Sci Signaljournal_title
Science signalingauthors
Zhang D,Yang S,Toledo EM,Gyllborg D,Saltó C,Carlos Villaescusa J,Arenas Edoi
10.1126/scisignal.aal4165subject
Has Abstractpub_date
2017-08-22 00:00:00issue
493eissn
1945-0877issn
1937-9145pii
10/493/eaal4165journal_volume
10pub_type
杂志文章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
更新日期:2010-09-28 00:00:00
abstract::The C-terminal guanine nucleotide exchange factor (GEF) module of Trio (TrioC) transfers signals from the Gαq/11 subfamily of heterotrimeric G proteins to the small guanosine triphosphatase (GTPase) RhoA, enabling Gαq/11-coupled G protein-coupled receptors (GPCRs) to control downstream events, such as cell motility an...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aav2449
更新日期:2019-02-19 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::MicroRNAs (miRNAs), key posttranscriptional regulators of many biological processes, have been implicated in many diseases, including cancer. In a recent paper, Avraham and colleagues take a systems biology approach to determine whether and how miRNAs are involved in the regulation of oncogenic signaling networks down...
journal_title:Science signaling
pub_type: 评论,杂志文章,评审
doi:10.1126/scisignal.2002182
更新日期:2011-07-26 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::Epigenetic modifications, such as DNA cytosine methylation, contribute to the mechanisms underlying learning and memory by coordinating adaptive gene expression and neuronal plasticity. Transcription-dependent plasticity regulated by DNA methylation includes synaptic plasticity and homeostatic synaptic scaling. Memory...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaf5642
更新日期:2016-08-23 00:00:00
abstract::Regulatory T (T(reg)) cells are a unique CD4(+) T cell lineage that plays a crucial role in the maintenance of immunological tolerance. The Forkhead box transcription factor Foxp3 is critically involved in T(reg) cell development and responsible for determining the suppressive function of these cells. The majority of ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2001783
更新日期:2011-02-01 00:00:00
abstract::We previously developed a web tool, Transcriptomine, to explore expression profiling data sets involving small-molecule or genetic manipulations of nuclear receptor signaling pathways. We describe advances in biocuration, query interface design, and data visualization that enhance the discovery of uncharacterized biol...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aah6275
更新日期:2017-04-25 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::Interleukin-2 (IL-2)-inducible T cell kinase (ITK) mediates T cell receptor (TCR) signaling primarily to stimulate the production of cytokines, such as IL-4, IL-5, and IL-13, from T helper 2 (TH2) cells. Compared to wild-type mice, ITK knockout mice are resistant to asthma and exhibit reduced lung inflammation and dec...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aab0949
更新日期:2015-12-01 00:00:00
abstract::The hypoxia inducible factors (HIFs) and CCAAT/enhancer binding protein alpha (C/EBP alpha) are transcription factors that mediate adaptive responses to hypoxia and control aspects of energy metabolism, respectively. New evidence suggests that when HIF-1 alpha and C/EBP alpha interact, they bring about reciprocal func...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.143jc2
更新日期:2008-10-28 00:00:00
abstract::Cellular proliferation, differentiation, and morphogenesis are shaped by multiple signaling cascades, and their dysregulation plays an integral role in cancer progression. Three cascades that contribute to oncogenic potential are those mediated by Wnt proteins and the receptor Frizzled (FZD), growth factor receptor ty...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aao4220
更新日期:2018-02-27 00:00:00
abstract::The complexity of the signaling network that is initiated by members of the transforming growth factor-beta (TGF-beta) superfamily continues to increase. In addition, Smads, which were originally identified as key transducers of TGF-beta signals, are beginning to emerge as players in other TGF-beta-independent process...
journal_title:Science signaling
pub_type: 社论
doi:10.1126/scisignal.146eg8
更新日期:2008-11-18 00:00:00
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
更新日期:2012-04-17 00:00:00
abstract::Staphylococcus aureus is an important opportunistic human pathogen that is highly resistant to osmotic stresses. To survive an increase in osmolarity, bacteria immediately take up potassium ions and small organic compounds known as compatible solutes. The second messenger cyclic diadenosine monophosphate (c-di-AMP) re...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaf7279
更新日期:2016-08-16 00:00:00
abstract::Endothelial cell dysfunction, characterized by a diminished response to endothelial cell-dependent vasodilators, is a hallmark of hypertension. TRPV4 channels play a major role in endothelial-dependent vasodilation, a function mediated by local Ca(2+) influx through clusters of functionally coupled TRPV4 channels rath...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2005052
更新日期:2014-07-08 00:00:00
abstract::Clinical response to chimeric antigen receptor (CAR) T cell therapy is correlated with CAR T cell persistence, especially for CAR T cells that target CD19+ hematologic malignancies. 4-1BB-costimulated CAR (BBζ) T cells exhibit longer persistence after adoptive transfer than do CD28-costimulated CAR (28ζ) T cells. 4-1B...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aay8248
更新日期:2020-03-31 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::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
更新日期:2017-10-03 00:00:00
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
更新日期:2011-10-25 00:00:00
abstract::The symbiotic interaction between Rhizobium bacteria and legume plants leads to the induction of a new developmental program: the formation of nitrogen-fixing root nodules. Nodulation is triggered by specific bacterial signals, the Nod factors, and integrates plant developmental regulatory pathways to reactivate diffe...
journal_title:Science signaling
pub_type: 杂志文章,评审
doi:10.1126/scisignal.149re11
更新日期:2008-12-09 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::The CLAVATA (CLV) and flagellin (flg) signaling pathways act through peptide ligands and closely related plasma membrane-localized receptor-like kinases (RLKs). The plant peptide CLV3 regulates stem cell homeostasis, whereas the bacterial flg22 peptide elicits defense responses. We applied multiparameter fluorescence ...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aab0598
更新日期:2015-08-04 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::The endoplasmic reticulum (ER) has emerged as a critical regulator of cell survival. IRE1 is a transmembrane protein with kinase and RNase activities that is localized to the ER and that promotes resistance to ER stress. We showed a mechanism by which IRE1 conferred protection against ER stress-mediated cell death. IR...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aaa0341
更新日期:2015-06-23 00:00:00
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
更新日期:2013-01-08 00:00:00
abstract::Cytotoxic lymphocytes share the presence of the activating receptor NK receptor group 2, member D (NKG2D) and the signaling-competent adaptor DNAX-activating protein 10 (DAP10), which together play an important role in antitumor immune surveillance. Ligand stimulation induces the internalization of NKG2D-DAP10 complex...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.aab2724
更新日期:2015-10-27 00:00:00
abstract::Precise regulation of nuclear factor κB (NF-κB) signaling is crucial for normal immune responses, and defective NF-κB activity underlies a range of immunodeficiencies. NF-κB is activated through two signaling cascades: the classical and noncanonical pathways. The classical pathway requires inhibitor of κB kinase β (IK...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2004557
更新日期:2014-02-04 00:00:00
abstract::A major endpoint of the canonical Wnt signaling pathway is a change in the transcription of target genes. The transcription factors lymphoid enhancer factor (LEF) and T cell factor (TCF) serve as the main gatekeepers of these changes by selecting genes to be targeted by the transcriptional coregulator beta-catenin and...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.139pe43
更新日期:2008-09-30 00:00:00
abstract::Phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins play essential roles in DNA-based and RNA-based processes, such as the response to DNA damage, messenger RNA (mRNA) quality control, transcription, and translation, where they contribute to the maintenance of genome integrity and accurate gene...
journal_title:Science signaling
pub_type: 杂志文章
doi:10.1126/scisignal.2000468
更新日期:2010-04-06 00:00:00