Heterodimerization of p45-p75 modulates p75 signaling: structural basis and mechanism of action.

Abstract:

:The p75 neurotrophin receptor, a member of the tumor necrosis factor receptor superfamily, is required as a co-receptor for the Nogo receptor (NgR) to mediate the activity of myelin-associated inhibitors such as Nogo, MAG, and OMgp. p45/NRH2/PLAIDD is a p75 homologue and contains a death domain (DD). Here we report that p45 markedly interferes with the function of p75 as a co-receptor for NgR. P45 forms heterodimers with p75 and thereby blocks RhoA activation and inhibition of neurite outgrowth induced by myelin-associated inhibitors. p45 binds p75 through both its transmembrane (TM) domain and DD. To understand the underlying mechanisms, we have determined the three-dimensional NMR solution structure of the intracellular domain of p45 and characterized its interaction with p75. We have identified the residues involved in such interaction by NMR and co-immunoprecipitation. The DD of p45 binds the DD of p75 by electrostatic interactions. In addition, previous reports suggested that Cys257 in the p75 TM domain is required for signaling. We found that the interaction of the cysteine 58 of p45 with the cysteine 257 of p75 within the TM domain is necessary for p45-p75 heterodimerization. These results suggest a mechanism involving both the TM domain and the DD of p45 to regulate p75-mediated signaling.

journal_name

PLoS Biol

journal_title

PLoS biology

authors

Vilar M,Sung TC,Chen Z,García-Carpio I,Fernandez EM,Xu J,Riek R,Lee KF

doi

10.1371/journal.pbio.1001918

subject

Has Abstract

pub_date

2014-08-05 00:00:00

pages

e1001918

issue

8

eissn

1544-9173

issn

1545-7885

pii

PBIOLOGY-D-14-01553

journal_volume

12

pub_type

杂志文章
  • Cell-by-cell dissection of gene expression and chromosomal interactions reveals consequences of nuclear reorganization.

    abstract::The functional consequences of long-range nuclear reorganization were studied in a cell-by-cell analysis of gene expression and long-range chromosomal interactions in the Drosophila eye and eye imaginal disk. Position-effect variegation was used to stochastically perturb gene expression and probe nuclear reorganizatio...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0030067

    authors: Harmon B,Sedat J

    更新日期:2005-03-01 00:00:00

  • Identification and functional characterization of N-terminally acetylated proteins in Drosophila melanogaster.

    abstract::Protein modifications play a major role for most biological processes in living organisms. Amino-terminal acetylation of proteins is a common modification found throughout the tree of life: the N-terminus of a nascent polypeptide chain becomes co-translationally acetylated, often after the removal of the initiating me...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1000236

    authors: Goetze S,Qeli E,Mosimann C,Staes A,Gerrits B,Roschitzki B,Mohanty S,Niederer EM,Laczko E,Timmerman E,Lange V,Hafen E,Aebersold R,Vandekerckhove J,Basler K,Ahrens CH,Gevaert K,Brunner E

    更新日期:2009-11-01 00:00:00

  • Sex and suicide: The curious case of Toll-like receptors.

    abstract::During in vitro fertilisation (IVF), pharmacological activation of the murine X chromosome-encoded receptor proteins Toll-like receptor (TLR) 7 and TLR8 reportedly results in male-biased litters by selectively disrupting the motility of X-bearing sperm cells. Thus-in the context of agonist treatment during IVF-these r...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000663

    authors: Navarro-Costa PA,Molaro A,Misra CS,Meiklejohn CD,Ellis PJ

    更新日期:2020-03-23 00:00:00

  • Ionotropic Chemosensory Receptors Mediate the Taste and Smell of Polyamines.

    abstract::The ability to find and consume nutrient-rich diets for successful reproduction and survival is fundamental to animal life. Among the nutrients important for all animals are polyamines, a class of pungent smelling compounds required in numerous cellular and organismic processes. Polyamine deficiency or excess has detr...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1002454

    authors: Hussain A,Zhang M,Üçpunar HK,Svensson T,Quillery E,Gompel N,Ignell R,Grunwald Kadow IC

    更新日期:2016-05-04 00:00:00

  • GPCRs Direct Germline Development and Somatic Gonad Function in Planarians.

    abstract::Planarians display remarkable plasticity in maintenance of their germline, with the ability to develop or dismantle reproductive tissues in response to systemic and environmental cues. Here, we investigated the role of G protein-coupled receptors (GPCRs) in this dynamic germline regulation. By genome-enabled receptor ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1002457

    authors: Saberi A,Jamal A,Beets I,Schoofs L,Newmark PA

    更新日期:2016-05-10 00:00:00

  • Drosophila spastin regulates synaptic microtubule networks and is required for normal motor function.

    abstract::The most common form of human autosomal dominant hereditary spastic paraplegia (AD-HSP) is caused by mutations in the SPG4 (spastin) gene, which encodes an AAA ATPase closely related in sequence to the microtubule-severing protein Katanin. Patients with AD-HSP exhibit degeneration of the distal regions of the longest ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0020429

    authors: Sherwood NT,Sun Q,Xue M,Zhang B,Zinn K

    更新日期:2004-12-01 00:00:00

  • Birds, blooms, and evolving diversity.

    abstract::In this Open Highlight, Senior Editor Lauren Richardson features exciting new Open Access research into how species evolve their characteristic traits. ...

    journal_title:PLoS biology

    pub_type: 评论,杂志文章

    doi:10.1371/journal.pbio.3000020

    authors: Richardson LA

    更新日期:2018-10-04 00:00:00

  • Gametogenesis in malaria parasites is mediated by the cGMP-dependent protein kinase.

    abstract::Malaria parasite transmission requires differentiation of male and female gametocytes into gametes within a mosquito following a blood meal. A mosquito-derived molecule, xanthurenic acid (XA), can trigger gametogenesis, but the signalling events controlling this process in the human malaria parasite Plasmodium falcipa...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0060139

    authors: McRobert L,Taylor CJ,Deng W,Fivelman QL,Cummings RM,Polley SD,Billker O,Baker DA

    更新日期:2008-06-03 00:00:00

  • Oxidative stress inactivates cobalamin-independent methionine synthase (MetE) in Escherichia coli.

    abstract::In nature, Escherichia coli are exposed to harsh and non-ideal growth environments-nutrients may be limiting, and cells are often challenged by oxidative stress. For E. coli cells confronting these realities, there appears to be a link between oxidative stress, methionine availability, and the enzyme that catalyzes th...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0020336

    authors: Hondorp ER,Matthews RG

    更新日期:2004-11-01 00:00:00

  • Role of a novel PH-kinase domain interface in PKB/Akt regulation: structural mechanism for allosteric inhibition.

    abstract::Protein kinase B (PKB/Akt) belongs to the AGC superfamily of related serine/threonine protein kinases. It is a key regulator downstream of various growth factors and hormones and is involved in malignant transformation and chemo-resistance. Full-length PKB protein has not been crystallised, thus studying the molecular...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1000017

    authors: Calleja V,Laguerre M,Parker PJ,Larijani B

    更新日期:2009-01-20 00:00:00

  • ATRX affects the repair of telomeric DSBs by promoting cohesion and a DAXX-dependent activity.

    abstract::Alpha thalassemia/mental retardation syndrome X-linked chromatin remodeler (ATRX), a DAXX (death domain-associated protein) interacting protein, is often lost in cells using the alternative lengthening of telomeres (ALT) pathway, but it is not known how ATRX loss leads to ALT. We report that ATRX deletion from mouse c...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000594

    authors: Lovejoy CA,Takai K,Huh MS,Picketts DJ,de Lange T

    更新日期:2020-01-02 00:00:00

  • The Genomic Standards Consortium.

    abstract::A vast and rich body of information has grown up as a result of the world's enthusiasm for 'omics technologies. Finding ways to describe and make available this information that maximise its usefulness has become a major effort across the 'omics world. At the heart of this effort is the Genomic Standards Consortium (G...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001088

    authors: Field D,Amaral-Zettler L,Cochrane G,Cole JR,Dawyndt P,Garrity GM,Gilbert J,Glöckner FO,Hirschman L,Karsch-Mizrachi I,Klenk HP,Knight R,Kottmann R,Kyrpides N,Meyer F,San Gil I,Sansone SA,Schriml LM,Sterk P,Tatusova T

    更新日期:2011-06-01 00:00:00

  • Using structural information to change the phosphotransfer specificity of a two-component chemotaxis signalling complex.

    abstract::Two-component signal transduction pathways comprising histidine protein kinases (HPKs) and their response regulators (RRs) are widely used to control bacterial responses to environmental challenges. Some bacteria have over 150 different two-component pathways, and the specificity of the phosphotransfer reactions withi...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1000306

    authors: Bell CH,Porter SL,Strawson A,Stuart DI,Armitage JP

    更新日期:2010-02-09 00:00:00

  • Bistable expression of virulence genes in salmonella leads to the formation of an antibiotic-tolerant subpopulation.

    abstract::Phenotypic heterogeneity can confer clonal groups of organisms with new functionality. A paradigmatic example is the bistable expression of virulence genes in Salmonella typhimurium, which leads to phenotypically virulent and phenotypically avirulent subpopulations. The two subpopulations have been shown to divide lab...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001928

    authors: Arnoldini M,Vizcarra IA,Peña-Miller R,Stocker N,Diard M,Vogel V,Beardmore RE,Hardt WD,Ackermann M

    更新日期:2014-08-19 00:00:00

  • Cargo and dynamin regulate clathrin-coated pit maturation.

    abstract::Total internal reflection fluorescence microscopy (TIR-FM) has become a powerful tool for studying clathrin-mediated endocytosis. However, due to difficulties in tracking and quantifying their heterogeneous dynamic behavior, detailed analyses have been restricted to a limited number of selected clathrin-coated pits (C...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1000057

    authors: Loerke D,Mettlen M,Yarar D,Jaqaman K,Jaqaman H,Danuser G,Schmid SL

    更新日期:2009-03-17 00:00:00

  • The pregnant myometrium is epigenetically activated at contractility-driving gene loci prior to the onset of labor in mice.

    abstract::During gestation, uterine smooth muscle cells transition from a state of quiescence to one of contractility, but the molecular mechanisms underlying this transition at a genomic level are not well-known. To better understand these events, we evaluated the epigenetic landscape of the mouse myometrium during the pregnan...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000710

    authors: Shchuka VM,Abatti LE,Hou H,Khader N,Dorogin A,Wilson MD,Shynlova O,Mitchell JA

    更新日期:2020-07-15 00:00:00

  • GAD2 on chromosome 10p12 is a candidate gene for human obesity.

    abstract::The gene GAD2 encoding the glutamic acid decarboxylase enzyme (GAD65) is a positional candidate gene for obesity on Chromosome 10p11-12, a susceptibility locus for morbid obesity in four independent ethnic populations. GAD65 catalyzes the formation of gamma-aminobutyric acid (GABA), which interacts with neuropeptide Y...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0000068

    authors: Boutin P,Dina C,Vasseur F,Dubois S,Corset L,Séron K,Bekris L,Cabellon J,Neve B,Vasseur-Delannoy V,Chikri M,Charles MA,Clement K,Lernmark A,Froguel P

    更新日期:2003-12-01 00:00:00

  • Why is congenital Zika syndrome asymmetrically distributed among human populations?

    abstract::Zika virus (ZIKV) is a health burden due to the severe neurological abnormalities that arise after congenital infection. Although multiple experimental studies have linked ZIKV with neural birth defects, the scientific community has not been able to fully explain why Congenital Zika Syndrome (CZS) was only apparent af...

    journal_title:PLoS biology

    pub_type: 杂志文章,评审

    doi:10.1371/journal.pbio.2006592

    authors: Barbeito-Andrés J,Schuler-Faccini L,Garcez PP

    更新日期:2018-08-24 00:00:00

  • Long-term relationships between synaptic tenacity, synaptic remodeling, and network activity.

    abstract::Synaptic plasticity is widely believed to constitute a key mechanism for modifying functional properties of neuronal networks. This belief implicitly implies, however, that synapses, when not driven to change their characteristics by physiologically relevant stimuli, will maintain these characteristics over time. How ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1000136

    authors: Minerbi A,Kahana R,Goldfeld L,Kaufman M,Marom S,Ziv NE

    更新日期:2009-06-23 00:00:00

  • The virtual cell animation collection: tools for teaching molecular and cellular biology.

    abstract::A cell is a minifactory in which structures and molecules are assembled, rearranged, disassembled, packaged, sorted, and transported. Because cellular structures and molecules are invisible to the human eye, students often have difficulty conceptualizing the dynamic nature of cells that function at multiple scales acr...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1002118

    authors: Reindl KM,White AR,Johnson C,Vender B,Slator BM,McClean P

    更新日期:2015-04-09 00:00:00

  • Laws of concatenated perception: Vision goes for novelty, decisions for perseverance.

    abstract::Every instant of perception depends on a cascade of brain processes calibrated to the history of sensory and decisional events. In the present work, we show that human visual perception is constantly shaped by two contrasting forces exerted by sensory adaptation and past decisions. In a series of experiments, we used ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000144

    authors: Pascucci D,Mancuso G,Santandrea E,Della Libera C,Plomp G,Chelazzi L

    更新日期:2019-03-05 00:00:00

  • N-wasp is essential for the negative regulation of B cell receptor signaling.

    abstract::Negative regulation of receptor signaling is essential for controlling cell activation and differentiation. In B-lymphocytes, the down-regulation of B-cell antigen receptor (BCR) signaling is critical for suppressing the activation of self-reactive B cells; however, the mechanism underlying the negative regulation of ...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001704

    authors: Liu C,Bai X,Wu J,Sharma S,Upadhyaya A,Dahlberg CI,Westerberg LS,Snapper SB,Zhao X,Song W

    更新日期:2013-11-01 00:00:00

  • Not just a theory--the utility of mathematical models in evolutionary biology.

    abstract::Progress in science often begins with verbal hypotheses meant to explain why certain biological phenomena exist. An important purpose of mathematical models in evolutionary research, as in many other fields, is to act as “proof-of-concept” tests of the logic in verbal explanations, paralleling the way in which empiric...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1002017

    authors: Servedio MR,Brandvain Y,Dhole S,Fitzpatrick CL,Goldberg EE,Stern CA,Van Cleve J,Yeh DJ

    更新日期:2014-12-09 00:00:00

  • Role of translational coupling in robustness of bacterial chemotaxis pathway.

    abstract::Chemotaxis allows bacteria to colonize their environment more efficiently and to find optimal growth conditions, and is consequently under strong evolutionary selection. Theoretical and experimental analyses of bacterial chemotaxis suggested that the pathway has been evolutionarily optimized to produce robust output u...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1000171

    authors: Løvdok L,Bentele K,Vladimirov N,Müller A,Pop FS,Lebiedz D,Kollmann M,Sourjik V

    更新日期:2009-08-01 00:00:00

  • Oocyte Polarization Is Coupled to the Chromosomal Bouquet, a Conserved Polarized Nuclear Configuration in Meiosis.

    abstract::The source of symmetry breaking in vertebrate oocytes is unknown. Animal-vegetal oocyte polarity is established by the Balbiani body (Bb), a conserved structure found in all animals examined that contains an aggregate of specific mRNAs, proteins, and organelles. The Bb specifies the oocyte vegetal pole, which is key t...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1002335

    authors: Elkouby YM,Jamieson-Lucy A,Mullins MC

    更新日期:2016-01-07 00:00:00

  • Basic math in monkeys and college students.

    abstract::Adult humans possess a sophisticated repertoire of mathematical faculties. Many of these capacities are rooted in symbolic language and are therefore unlikely to be shared with nonhuman animals. However, a subset of these skills is shared with other animals, and this set is considered a cognitive vestige of our common...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.0050328

    authors: Cantlon JF,Brannon EM

    更新日期:2007-12-01 00:00:00

  • Smooth muscle tension induces invasive remodeling of the zebrafish intestine.

    abstract::The signals that initiate cell invasion are not well understood, but there is increasing evidence that extracellular physical signals play an important role. Here we show that epithelial cell invasion in the intestine of zebrafish meltdown (mlt) mutants arises in response to unregulated contractile tone in the surroun...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.1001386

    authors: Seiler C,Davuluri G,Abrams J,Byfield FJ,Janmey PA,Pack M

    更新日期:2012-01-01 00:00:00

  • Nucleotide de novo synthesis increases breast cancer stemness and metastasis via cGMP-PKG-MAPK signaling pathway.

    abstract::Metabolic reprogramming to fulfill the biosynthetic and bioenergetic demands of cancer cells has aroused great interest in recent years. However, metabolic reprogramming for cancer metastasis has not been well elucidated. Here, we screened a subpopulation of breast cancer cells with highly metastatic capacity to the l...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000872

    authors: Lv Y,Wang X,Li X,Xu G,Bai Y,Wu J,Piao Y,Shi Y,Xiang R,Wang L

    更新日期:2020-11-13 00:00:00

  • Correction: Song playbacks demonstrate slower evolution of song discrimination in birds from Amazonia than from temperate North America.

    abstract::[This corrects the article DOI: 10.1371/journal.pbio.3000478.]. ...

    journal_title:PLoS biology

    pub_type: 已发布勘误

    doi:10.1371/journal.pbio.3000568

    authors: PLOS Biology Staff.

    更新日期:2019-11-13 00:00:00

  • mRNA association by aminoacyl tRNA synthetase occurs at a putative anticodon mimic and autoregulates translation in response to tRNA levels.

    abstract::Aminoacyl-tRNA synthetases (aaRSs) are well studied for their role in binding and charging tRNAs with cognate amino acids. Recent RNA interactome studies had suggested that these enzymes can also bind polyadenylated RNAs. Here, we explored the mRNA repertoire bound by several yeast aaRSs. RNA immunoprecipitation (RIP)...

    journal_title:PLoS biology

    pub_type: 杂志文章

    doi:10.1371/journal.pbio.3000274

    authors: Levi O,Arava Y

    更新日期:2019-05-17 00:00:00