Abstract:
:The serotonin6 receptor (5-HT6R) is a promising target for treating cognitive deficits of schizophrenia often linked to alterations of neuronal development. This receptor controls neurodevelopmental processes, but the signaling mechanisms involved remain poorly understood. Using a proteomic strategy, we show that 5-HT6Rs constitutively interact with cyclin-dependent kinase 5 (Cdk5). Expression of 5-HT6Rs in NG108-15 cells induced neurite growth and expression of voltage-gated Ca(2+) channels, two hallmarks of neuronal differentiation. 5-HT6R-elicited neurite growth was agonist independent and prevented by the 5-HT6R antagonist SB258585, which behaved as an inverse agonist. Moreover, it required receptor phosphorylation at Ser350 by Cdk5 and Cdc42 activity. Supporting a role of native 5-HT6Rs in neuronal differentiation, neurite growth of primary neurons was reduced by SB258585, by silencing 5-HT6R expression or by mutating Ser350 into alanine. These results reveal a functional interplay between Cdk5 and a G protein-coupled receptor to control neuronal differentiation.
journal_name
Nat Chem Bioljournal_title
Nature chemical biologyauthors
Duhr F,Déléris P,Raynaud F,Séveno M,Morisset-Lopez S,Mannoury la Cour C,Millan MJ,Bockaert J,Marin P,Chaumont-Dubel Sdoi
10.1038/nchembio.1547subject
Has Abstractpub_date
2014-07-01 00:00:00pages
590-7issue
7eissn
1552-4450issn
1552-4469pii
nchembio.1547journal_volume
10pub_type
杂志文章abstract::Methylation of nucleotides in ribosomal RNAs (rRNAs) is a ubiquitous feature that occurs in all living organisms. Identification of all enzymes responsible for rRNA methylation, as well as mapping of all modified rRNA residues, is now complete for a number of model species, such as Escherichia coli and Saccharomyces c...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio.2569
更新日期:2018-02-14 00:00:00
abstract::Higher plants resist the forces of gravity and powerful lateral forces through the cumulative strength of the walls that surround individual cells. These walls consist mainly of cellulose, noncellulosic polysaccharides and lignin, in proportions that depend upon the specific functions of the cell and its stage of deve...
journal_title:Nature chemical biology
pub_type: 杂志文章,评审
doi:10.1038/nchembio.439
更新日期:2010-10-01 00:00:00
abstract::The nematode Caenorhabditis elegans requires exogenous cholesterol to survive and its depletion leads to early developmental arrest. Thus, tight regulation of cholesterol storage and distribution within the organism is indispensable. Here, we present a novel class of C. elegans phosphorylated glycosphingolipids, phosp...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2347
更新日期:2017-06-01 00:00:00
abstract::MicroRNAs are evolutionarily conserved small, noncoding RNAs that regulate diverse biological processes. Due to their essential regulatory roles, microRNA biogenesis is tightly regulated, where protein factors are often found to interact with specific primary and precursor microRNAs for regulation. Here, using NMR rel...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-020-00667-5
更新日期:2021-01-01 00:00:00
abstract::ADP-ribosylation (ADPr) is a biologically and clinically important post-translational modification, but little is known about the amino acids it targets on cellular proteins. Here we present a proteomic approach for direct in vivo identification and quantification of ADPr sites on histones. We have identified 12 uniqu...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2180
更新日期:2016-12-01 00:00:00
abstract::Mycobacterium tuberculosis and Yersinia pestis, the causative agents of tuberculosis and plague, respectively, are pathogens with serious ongoing impact on global public health and potential use as agents of bioterrorism. Both pathogens have iron acquisition systems based on siderophores, secreted iron-chelating compo...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio706
更新日期:2005-06-01 00:00:00
abstract::The rise of antibiotic resistance demands the acceleration of molecular diversification strategies to inspire new chemical entities for antibiotic medicines. We report here on the large-scale engineering of ribosomally synthesized and post-translationally modified antimicrobial peptides carrying the ring-forming amino...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0250-5
更新日期:2019-05-01 00:00:00
abstract::Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2251
更新日期:2017-02-01 00:00:00
abstract::The catalytic activity of many protein kinases is controlled by conformational changes of a conserved Asp-Phe-Gly (DFG) motif. We used an infrared probe to track the DFG motif of the mitotic kinase Aurora A (AurA) and found that allosteric activation by the spindle-associated protein Tpx2 involves an equilibrium shift...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2296
更新日期:2017-04-01 00:00:00
abstract::More than 30 years ago, a calcium-dependent enzyme activity was described that generates N-acyl phosphatidylethanolamines (NAPEs), which are precursors for N-acyl ethanolamine (NAE) lipid transmitters, including the endocannabinoid anandamide. The identity of this calcium-dependent N-acyltransferase (Ca-NAT) has remai...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2127
更新日期:2016-09-01 00:00:00
abstract::Beyond established roles in collagen biosynthesis, hypoxic signaling and fatty acid metabolism, recent reports have now revealed roles for human 2-oxoglutarate-dependent oxygenases in histone and nucleic acid demethylation and in signaling protein hydroxylation. The emerging role of these oxygenases in enabling a mult...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio0308-152
更新日期:2008-03-01 00:00:00
abstract::Proteoglycans are complex glycoconjugates that regulate critical biological pathways in all higher organisms. Bikunin, the simplest proteoglycan, with a single glycosaminoglycan chain, is a serine protease inhibitor used to treat acute pancreatitis. Unlike nucleic acids and proteins, whose synthesis is template driven...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.673
更新日期:2011-10-09 00:00:00
abstract::RNA capping and decapping are thought to be distinctive features of eukaryotes. The redox cofactor NAD was recently discovered to be attached to small regulatory RNAs in bacteria in a cap-like manner, and Nudix hydrolase NudC was found to act as a NAD-decapping enzyme in vitro and in vivo. Here, crystal structures of ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2132
更新日期:2016-09-01 00:00:00
abstract::Using linewidth and spinning sideband intensities of lipid hydrocarbon chain resonances in proton magic angle spinning NMR spectra, we detected the temperature-dependent phase state of naturally occurring lipids of intact influenza virus without exogenous probes. Increasingly, below 41 degrees C ordered and disordered...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.77
更新日期:2008-04-01 00:00:00
abstract::Excessive aggregation of proteins has a major impact on cell fate and is a hallmark of amyloid diseases in humans. To resolve insoluble deposits and to maintain protein homeostasis, all cells use dedicated protein disaggregation, protein folding and protein degradation factors. Despite intense recent research, the und...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1931
更新日期:2015-11-01 00:00:00
abstract::Regulation of gene expression in response to the changing environment is critical for cell survival. For instance, binding of macrolide antibiotics to the ribosome promotes translation arrest at the leader open reading frames ermCL and ermBL, which is necessary for inducing the antibiotic resistance genes ermC and erm...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1998
更新日期:2016-03-01 00:00:00
abstract::Accumulation of unfolded proteins within the endoplasmic reticulum (ER) of eukaryotic cells leads to an unfolded protein response (UPR) that either restores homeostasis or commits the cells to apoptosis. Tools traditionally used to study the UPR are proapoptotic and thus confound analysis of long-term cellular respons...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1638
更新日期:2014-11-01 00:00:00
abstract::Enzymatic incorporation of a halogen atom is a common feature in the biosyntheses of more than 4,500 natural products. Halogenation of unactivated carbon centers in the biosyntheses of several compounds of nonribosomal peptide origin is carried out by a class of mononuclear nonheme iron enzymes that require alpha-keto...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio856
更新日期:2007-02-01 00:00:00
abstract::Naturally produced polybrominated diphenyl ethers (PBDEs) pervade the marine environment and structurally resemble toxic man-made brominated flame retardants. PBDEs bioaccumulate in marine animals and are likely transferred to the human food chain. However, the biogenic basis for PBDE production in one of their most p...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2330
更新日期:2017-05-01 00:00:00
abstract::Lipid rafts in plasma membranes have emerged as possible platforms for the entry of HIV and other viruses into cells. However, little is known about how lipid phase heterogeneity contributes to viral entry because of the fine-grained and still poorly understood complexity of biological membranes. We used model systems...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1800
更新日期:2015-06-01 00:00:00
abstract::The eukaryotic replicative DNA polymerases (Pol α, δ and ɛ) and the major DNA mutagenesis enzyme Pol ζ contain two conserved cysteine-rich metal-binding motifs (CysA and CysB) in the C-terminal domain (CTD) of their catalytic subunits. Here we demonstrate by in vivo and in vitro approaches the presence of an essential...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.721
更新日期:2011-11-27 00:00:00
abstract::N(1)-Methyladenosine (m(1)A) is a prevalent post-transcriptional RNA modification, yet little is known about its abundance, topology and dynamics in mRNA. Here, we show that m(1)A is prevalent in Homo sapiens mRNA, which shows an m(1)A/A ratio of ∼0.02%. We develop the m(1)A-ID-seq technique, based on m(1)A immunoprec...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2040
更新日期:2016-05-01 00:00:00
abstract::We document a new dimension of surface recognition in which communication is controlled through the collective behavior of lipids. Membrane cholesterol induces a tilt in glycolipid receptor headgroup, resulting in loss of access for ligand binding. This property appears to organize erythrocyte blood group presentation...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.551
更新日期:2011-05-01 00:00:00
abstract::Helical membrane proteins are typically assumed to attain stable transmembrane topologies immediately upon co-translational membrane insertion. Here we show that unassembled monomers of the small multidrug resistance (SMR) family exist in a dynamic equilibrium where the N-terminal transmembrane helix flips in and out ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/s41589-019-0356-9
更新日期:2019-10-01 00:00:00
abstract::Cell-permeable small molecules that inhibit their targets on fast timescales are powerful probes of cell-division mechanisms. Such inhibitors have been identified using phenotype-based screens with chemical libraries. However, the characteristics of compound libraries needed to effectively span cell-division phenotype...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio826
更新日期:2006-11-01 00:00:00
abstract::Linking bioactive compounds to their cellular targets is a central challenge in chemical biology. Here we report the mode of action of theonellamides, bicyclic peptides derived from marine sponges. We generated a chemical-genomic profile of theonellamide F using a collection of fission yeast strains in which each open...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.387
更新日期:2010-07-01 00:00:00
abstract::Mitochondrial electron transport drives ATP synthesis but also generates reactive oxygen species, which are both cellular signals and damaging oxidants. Superoxide production by respiratory complex III is implicated in diverse signaling events and pathologies, but its role remains controversial. Using high-throughput ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1910
更新日期:2015-11-01 00:00:00
abstract::The structure-specific nuclease human flap endonuclease-1 (hFEN1) plays a key role in DNA replication and repair and may be of interest as an oncology target. We present the crystal structure of inhibitor-bound hFEN1, which shows a cyclic N-hydroxyurea bound in the active site coordinated to two magnesium ions. Three ...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.2148
更新日期:2016-10-01 00:00:00
abstract::Kinase inhibitors are important cancer drugs, but they tend to display limited target specificity, and their target profiles are often challenging to rationalize in terms of molecular mechanism. Here we report that the clinical kinase inhibitor bosutinib recognizes its kinase targets by engaging a pair of conserved st...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1404
更新日期:2014-02-01 00:00:00
abstract::The P1B-ATPases, which couple cation transport across membranes to ATP hydrolysis, are central to metal homeostasis in all organisms. An important feature of P1B-ATPases is the presence of soluble metal binding domains (MBDs) that regulate transport activity. Only one type of MBD has been characterized extensively, bu...
journal_title:Nature chemical biology
pub_type: 杂志文章
doi:10.1038/nchembio.1863
更新日期:2015-09-01 00:00:00