Adenosine receptor A2A-R contributes to motoneuron survival by transactivating the tyrosine kinase receptor TrkB.

Abstract:

:Neurotrophins are potent survival factors for developing and injured neurons. However, they are not being used to treat neurodegenerative diseases because of difficulties in administration and numerous side effects that have been encountered in previous clinical trials. Their biological activities use Trk (tropomyosin-related kinase) transmembrane tyrosine kinases. Therefore, one alternative approach is to use transactivation pathways such as adenosine 2A receptor agonists, which can activate Trk receptor signaling independent of neurotrophin binding. However, the relevance in vivo and applicability of these transactivation events during neurodegenerative and injury conditions have never been extensively studied. Here we demonstrate that motoneuron survival after facial nerve lesioning is significantly enhanced by transactivation of Trk receptor tyrosine kinases by adenosine agonists. Moreover, survival of motoneurons directly required the activation of the BDNF receptor TrkB and an increase in Akt (AKT8 virus oncogene cellular homolog) activity. The ability of small molecules to activate a trophic response by using Trk signaling provides a unique mechanism to promote survival signals in motoneurons and suggests new strategies for using transactivation in neurodegenerative diseases.

authors

Wiese S,Jablonka S,Holtmann B,Orel N,Rajagopal R,Chao MV,Sendtner M

doi

10.1073/pnas.0705267104

subject

Has Abstract

pub_date

2007-10-23 00:00:00

pages

17210-5

issue

43

eissn

0027-8424

issn

1091-6490

pii

0705267104

journal_volume

104

pub_type

杂志文章
  • Inhibition of tissue damage by the arachidonate lipoxygenase inhibitor BW755C.

    abstract::The effects of three anti-inflammatory drugs, which interfere with arachidonic acid transformation by three different enzymes, have been compared by using a simple model of tissue damage and foreign body rejection. In groups of control rats, subcutaneously implanted polyester sponges were rejected after a mean of 12 d...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.9.2890

    authors: Higgs GA,Mugridge KG,Moncada S,Vane JR

    更新日期:1984-05-01 00:00:00

  • Huntingtin-associated protein (HAP1): discrete neuronal localizations in the brain resemble those of neuronal nitric oxide synthase.

    abstract::Huntington disease stems from a mutation of the protein huntingtin and is characterized by selective loss of discrete neuronal populations in the brain. Despite a massive loss of neurons in the corpus striatum, NO-generating neurons are intact. We recently identified a brain-specific protein that associates with hunti...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.10.4839

    authors: Li XJ,Sharp AH,Li SH,Dawson TM,Snyder SH,Ross CA

    更新日期:1996-05-14 00:00:00

  • Efficient UV-induced charge separation and recombination in an 8-oxoguanine-containing dinucleotide.

    abstract::During the early evolution of life, 8-oxo-7,8-dihydro-2'-deoxyguanosine (O) may have functioned as a proto-flavin capable of repairing cyclobutane pyrimidine dimers in DNA or RNA by photoinduced electron transfer using longer wavelength UVB radiation. To investigate the ability of O to act as an excited-state electron...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1404411111

    authors: Zhang Y,Dood J,Beckstead AA,Li XB,Nguyen KV,Burrows CJ,Improta R,Kohler B

    更新日期:2014-08-12 00:00:00

  • Free energy landscape for the binding process of Huperzine A to acetylcholinesterase.

    abstract::Drug-target residence time (t = 1/k(off), where k(off) is the dissociation rate constant) has become an important index in discovering better- or best-in-class drugs. However, little effort has been dedicated to developing computational methods that can accurately predict this kinetic parameter or related parameters, ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1301814110

    authors: Bai F,Xu Y,Chen J,Liu Q,Gu J,Wang X,Ma J,Li H,Onuchic JN,Jiang H

    更新日期:2013-03-12 00:00:00

  • Genetic requirements for mycobacterial survival during infection.

    abstract::Despite the importance of tuberculosis as a public health problem, we know relatively little about the molecular mechanisms used by the causative organism, Mycobacterium tuberculosis, to persist in the host. To define these mechanisms, we have mutated virtually every nonessential gene of M. tuberculosis and determined...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2134250100

    authors: Sassetti CM,Rubin EJ

    更新日期:2003-10-28 00:00:00

  • Temperature-compensated circadian clock in the pineal of Anolis.

    abstract::The pineal organ of the lizard Anolis carolinensis can be maintained for up to 10 days in superfused organ culture. During this time it synthesizes and releases melatonin into the medium flowing slowly over it. Collection of timed aliquots of medium and subsequent analysis for melatonin by radioimmunoassay reveal circ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.19.6119

    authors: Menaker M,Wisner S

    更新日期:1983-10-01 00:00:00

  • The time course and specificity of perceptual deterioration.

    abstract::Repeated within-day testing on a texture discrimination task leads to retinotopically specific decreases in performance. Although perceptual learning has been shown to be highly specific to the retinotopic location and characteristics of the trained stimulus, the specificity of perceptual deterioration has not been st...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0407866102

    authors: Mednick SC,Arman AC,Boynton GM

    更新日期:2005-03-08 00:00:00

  • Alkynyl sugar analogs for the labeling and visualization of glycoconjugates in cells.

    abstract::Developing tools for investigating the cellular activity of glycans will help to delineate the molecular basis for aberrant glycosylation in pathological processes such as cancer. Metabolic oligosaccharide engineering, which inserts sugar-reporting groups into cellular glycoconjugates, represents a powerful method for...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0611307104

    authors: Hsu TL,Hanson SR,Kishikawa K,Wang SK,Sawa M,Wong CH

    更新日期:2007-02-20 00:00:00

  • New class of transforming growth factors potentiated by epidermal growth factor: isolation from non-neoplastic tissues.

    abstract::Proteins potentiated by epidermal growth factor (EGF) to induce a transformed phenotype in non-neoplastic rat kidney fibroblasts in cell culture have been isolated from many non-neoplastic tissues of the adult mouse, including submaxillary gland, kidney, liver, muscle, heart, and brain. They resemble previously descri...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.9.5339

    authors: Roberts AB,Anzano MA,Lamb LC,Smith JM,Sporn MB

    更新日期:1981-09-01 00:00:00

  • The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton.

    abstract::Arf family GTP-binding proteins are best characterized as regulators of membrane traffic, but recent studies indicate an additional role in cytoskeletal organization. An Arf GTPase-activating protein of the centaurin beta family, ASAP1 (also known as centaurin beta4), binds Arf and two other known regulators of the ac...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.070552297

    authors: Randazzo PA,Andrade J,Miura K,Brown MT,Long YQ,Stauffer S,Roller P,Cooper JA

    更新日期:2000-04-11 00:00:00

  • Temperature-dependent solvation modulates the dimensions of disordered proteins.

    abstract::For disordered proteins, the dimensions of the chain are an important property that is sensitive to environmental conditions. We have used single-molecule Förster resonance energy transfer to probe the temperature-induced chain collapse of five unfolded or intrinsically disordered proteins. Because this behavior is se...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1313006111

    authors: Wuttke R,Hofmann H,Nettels D,Borgia MB,Mittal J,Best RB,Schuler B

    更新日期:2014-04-08 00:00:00

  • Lipid- and mechanosensitivities of sodium/hydrogen exchangers analyzed by electrical methods.

    abstract::Sodium/hydrogen exchangers (NHEs) are ubiquitous ion transporters that serve multiple cell functions. We have studied two mammalian isoforms, NHE1 (ubiquitous) and NHE3 (epithelial-specific), by measuring extracellular proton (H+) gradients during whole-cell patch clamp with perfusion of the cell interior. Maximal Na(...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0403930101

    authors: Fuster D,Moe OW,Hilgemann DW

    更新日期:2004-07-13 00:00:00

  • Identification of L-methionine-S-sulfoximine as the convulsant isomer of methionine sulfoximine.

    abstract::The convulsant agent methionine sulfoximine inhibits brain glutamine synthetase irreversibly and the inhibitor becomes bound to the active site of the enzyme as methionine sulfoximine phosphate. Only one of the four isomers of methionine sulfoximine, L-methionine-S-sulfoximine, inhibits glutamine synthetase. In the pr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.66.2.500

    authors: Rowe WB,Meister A

    更新日期:1970-06-01 00:00:00

  • Near-infrared fluorescent sensor for in vivo copper imaging in a murine Wilson disease model.

    abstract::Copper is an essential metal nutrient that is tightly regulated in the body because loss of its homeostasis is connected to severe diseases such as Menkes and Wilson diseases, Alzheimer's disease, prion disorders, and amyotrophic lateral sclerosis. The complex relationships between copper status and various stages of ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1113729109

    authors: Hirayama T,Van de Bittner GC,Gray LW,Lutsenko S,Chang CJ

    更新日期:2012-02-14 00:00:00

  • Genomic analysis of uncultured marine viral communities.

    abstract::Viruses are the most common biological entities in the oceans by an order of magnitude. However, very little is known about their diversity. Here we report a genomic analysis of two uncultured marine viral communities. Over 65% of the sequences were not significantly similar to previously reported sequences, suggestin...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.202488399

    authors: Breitbart M,Salamon P,Andresen B,Mahaffy JM,Segall AM,Mead D,Azam F,Rohwer F

    更新日期:2002-10-29 00:00:00

  • Induction of erythroid differentiation in murine virus infected eythroleukemia cells by highly polar compounds.

    abstract::Murine-virus-infected erythroleukemia cells cultured in a medium with dimethylsulfoxide or N,N-dimethylformamide are induced to differentiate to erythroid cells. A number of highly polar compounds have a similar effect in inducing erythroid differentiation of the virus-infected cells, as assayed by the appearance of h...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.72.3.1003

    authors: Tanaka M,Levy J,Terada M,Breslow R,Rifkind RA,Marks PA

    更新日期:1975-03-01 00:00:00

  • How collective asperity detachments nucleate slip at frictional interfaces.

    abstract::Sliding at a quasi-statically loaded frictional interface can occur via macroscopic slip events, which nucleate locally before propagating as rupture fronts very similar to fracture. We introduce a microscopic model of a frictional interface that includes asperity-level disorder, elastic interaction between local slip...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1906551116

    authors: de Geus TWJ,Popović M,Ji W,Rosso A,Wyart M

    更新日期:2019-11-26 00:00:00

  • Interleukin-1 deficiency prolongs ovarian lifespan in mice.

    abstract::Oocyte endowment dwindles away during prepubertal and adult life until menopause occurs, and apoptosis has been identified as a central mechanism responsible for oocyte elimination. A few recent reports suggest that uncontrolled inflammation may adversely affect ovarian reserve. We tested the possible role of the proi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1323955111

    authors: Uri-Belapolsky S,Shaish A,Eliyahu E,Grossman H,Levi M,Chuderland D,Ninio-Many L,Hasky N,Shashar D,Almog T,Kandel-Kfir M,Harats D,Shalgi R,Kamari Y

    更新日期:2014-08-26 00:00:00

  • Energies and kinetics of radical pairs involving bacteriochlorophyll and bacteriopheophytin in bacterial reaction centers.

    abstract::Absorbance changes reflecting the formation of a transient radical-pair state, P(F), were measured in reaction centers from Rhodopseudomonas sphaeroides under conditions that blocked electron transfer to a later carrier (a quinone, Q). The temperature dependence of the absorbance changes suggests that P(F) is an equil...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.2.957

    authors: Shuvalov VA,Parson WW

    更新日期:1981-02-01 00:00:00

  • Delineation of a molecularly distinct terminally differentiated memory CD8 T cell population.

    abstract::Memory CD8 T cells provide durable protection against diverse intracellular pathogens and can be broadly segregated into distinct circulating and tissue-resident populations. Paradigmatic studies have demonstrated that circulating memory cells can be further divided into effector memory (Tem) and central memory (Tcm) ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2008571117

    authors: Milner JJ,Nguyen H,Omilusik K,Reina-Campos M,Tsai M,Toma C,Delpoux A,Boland BS,Hedrick SM,Chang JT,Goldrath AW

    更新日期:2020-10-13 00:00:00

  • Positionally cloned human disease genes: patterns of evolutionary conservation and functional motifs.

    abstract::Positional cloning has already produced the sequences of more than 70 human genes associated with specific diseases. In addition to their medical importance, these genes are of interest as a set of human genes isolated solely on the basis of the phenotypic effect of the respective mutations. We analyzed the protein se...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.11.5831

    authors: Mushegian AR,Bassett DE Jr,Boguski MS,Bork P,Koonin EV

    更新日期:1997-05-27 00:00:00

  • Intramembrane charge movements and excitation- contraction coupling expressed by two-domain fragments of the Ca2+ channel.

    abstract::To investigate the molecular basis of the voltage sensor that triggers excitation-contraction (EC) coupling, the four-domain pore subunit of the dihydropyridine receptor (DHPR) was cut in the cytoplasmic linker between domains II and III. cDNAs for the I-II domain (alpha1S 1-670) and the III-IV domain (alpha1S 701-187...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.111001898

    authors: Ahern CA,Arikkath J,Vallejo P,Gurnett CA,Powers PA,Campbell KP,Coronado R

    更新日期:2001-06-05 00:00:00

  • Importance of free actin filament barbed ends for Arp2/3 complex function in platelets and fibroblasts.

    abstract::We investigated the effect of actin filament barbed end uncapping on Arp23 complex function both in vivo and in vitro. Arp23 complex redistributes rapidly and uniformly to the lamellar edge of activated wild-type platelets and fibroblasts but clusters in marginal actin filament clumps in gelsolin-null cells. Treatment...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.222652499

    authors: Falet H,Hoffmeister KM,Neujahr R,Italiano JE Jr,Stossel TP,Southwick FS,Hartwig JH

    更新日期:2002-12-24 00:00:00

  • Epidermal growth factor stimulates tyrosine phosphorylation in the neonatal mouse: association of a M(r) 55,000 substrate with the receptor.

    abstract::Administration of epidermal growth factor (EGF) to neonatal mice resulted in rapid tyrosine phosphorylation of a number of specific substrates in liver, kidney, lung, bladder, skin, and brain as detected by Western blot analysis of tissue homogenates with anti-phosphotyrosine antibodies. In the liver, three prominent ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.18.8477

    authors: Donaldson RW,Cohen S

    更新日期:1992-09-15 00:00:00

  • Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness.

    abstract::The human beta(2)-adrenergic receptor gene has multiple single-nucleotide polymorphisms (SNPs), but the relevance of chromosomally phased SNPs (haplotypes) is not known. The phylogeny and the in vitro and in vivo consequences of variations in the 5' upstream and ORF were delineated in a multiethnic reference populatio...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.97.19.10483

    authors: Drysdale CM,McGraw DW,Stack CB,Stephens JC,Judson RS,Nandabalan K,Arnold K,Ruano G,Liggett SB

    更新日期:2000-09-12 00:00:00

  • Stimulation by phospholipids of a protein-tyrosine-phosphatase containing two src homology 2 domains.

    abstract::PTP1C, a protein-tyrosine-phosphatase (protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48) containing two src homology 2 domains, is poorly active when assayed with various protein substrates in vitro. Its activity is stimulated > 1000-fold by anionic phospholipids when myelin basic protein or mitogen-activated ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.9.4251

    authors: Zhao Z,Shen SH,Fischer EH

    更新日期:1993-05-01 00:00:00

  • Serine protease autotransporters from Shigella flexneri and pathogenic Escherichia coli target a broad range of leukocyte glycoproteins.

    abstract::The serine protease autotransporters of Enterobacteriaceae (SPATEs) are secreted by pathogenic Gram-negative bacteria through the autotransporter pathway. We previously classified SPATE proteins into two classes: cytotoxic (class 1) and noncytotoxic (class 2). Here, we show that Pic, a class 2 SPATE protein produced b...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1101006108

    authors: Ruiz-Perez F,Wahid R,Faherty CS,Kolappaswamy K,Rodriguez L,Santiago A,Murphy E,Cross A,Sztein MB,Nataro JP

    更新日期:2011-08-02 00:00:00

  • A folding switch regulates interleukin 27 biogenesis and secretion of its α-subunit as a cytokine.

    abstract::A common design principle of heteromeric signaling proteins is the use of shared subunits. This allows encoding of complex messages while maintaining evolutionary flexibility. How cells regulate and control assembly of such composite signaling proteins remains an important open question. An example of particular compl...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1816698116

    authors: Müller SI,Friedl A,Aschenbrenner I,Esser-von Bieren J,Zacharias M,Devergne O,Feige MJ

    更新日期:2019-01-29 00:00:00

  • Replication of lambda dv plasmid in vitro promoted by purified lambda O and P proteins.

    abstract::An in vitro system for replication of lambda dv plasmid DNA has been constructed. This system consists of an ammonium sulfate fraction from Escherichia coli extract, exogenously added purified lambda O and P proteins, and lambda dv DNA in closed circular form. More than 85% of the added template DNA replicated semicon...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.79.24.7639

    authors: Tsurimoto T,Matsubara K

    更新日期:1982-12-01 00:00:00

  • C-terminal deletion mutant of pokeweed antiviral protein inhibits viral infection but does not depurinate host ribosomes.

    abstract::Pokeweed antiviral protein (PAP), a 29-kDa protein isolated from Phytolacca americana, inhibits translation by catalytically removing a specific adenine residue from the large rRNA of the 60S subunit of eukaryotic ribosomes. In addition to its ribosome-inactivating ability, PAP has potent antiviral activity against ma...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.8.3866

    authors: Tumer NE,Hwang DJ,Bonness M

    更新日期:1997-04-15 00:00:00