Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Structural basis for extracellular cis and trans RPTPσ signal competition in synaptogenesis.

ABSTRACT: Receptor protein tyrosine phosphatase sigma (RPTPσ) regulates neuronal extension and acts as a presynaptic nexus for multiple protein and proteoglycan interactions during synaptogenesis. Unknown mechanisms govern the shift in RPTPσ function, from outgrowth promotion to synaptic organization. Here, we report crystallographic, electron microscopic and small-angle X-ray scattering analyses, which reveal sufficient inter-domain flexibility in the RPTPσ extracellular region for interaction with both cis (same cell) and trans (opposite cell) ligands. Crystal structures of RPTPσ bound to its postsynaptic ligand TrkC detail an interaction surface partially overlapping the glycosaminoglycan-binding site. Accordingly, heparan sulphate and heparin oligomers compete with TrkC for RPTPσ binding in vitro and disrupt TrkC-dependent synaptic differentiation in neuronal co-culture assays. We propose that transient RPTPσ ectodomain emergence from the presynaptic proteoglycan layer allows capture by TrkC to form a trans-synaptic complex, the consequent reduction in RPTPσ flexibility potentiating interactions with additional ligands to orchestrate excitatory synapse formation.

SUBMITTER: Coles CH

PROVIDER: S-EPMC4239663 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Structural Basis for LAR-RPTP-Mediated Synaptogenesis.

Project description:Leukocyte common antigen-related protein tyrosine phosphatases (LAR-RPTPs) are cellular receptors of heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans that regulate neurite outgrowth and neuronal regeneration. LAR-RPTPs have also received particular attention as the major presynaptic hubs for synapse organization through selective binding to numerous postsynaptic adhesion partners. Recent structural studies on LAR-RPTP-mediated trans-synaptic adhesion complexes have provided significant insight into the molecular basis of their specific interactions, the key codes for their selective binding, as well as the higher-order clustering of LAR-RPTPs necessary for synaptogenic activity. In this review, we summarize the structures of LAR-RPTPs in complex with various postsynaptic adhesion partners and discuss the molecular mechanisms underlying LAR-RPTP-mediated synaptogenesis.

| S-EPMC6078854 | biostudies-literature

The biochemical and structural basis for trans-to-cis isomerization of retinoids in the chemistry of vision.

Project description:Recently, much progress has been made in elucidating the chemistry and metabolism of retinoids and carotenoids, as well as the structures of processing proteins related to vision. Carotenoids and their retinoid metabolites are isoprenoids, so only a limited number of chemical transformations are possible, and just a few of these occur naturally. Although there is an intriguing evolutionary conservation of the key components involved in the production and recycling of chromophores, these genes have also adapted to the specific requirements of insect and vertebrate vision. These 'ancestral footprints' in animal genomes bear witness to the common origin of the chemistry of vision, and will further stimulate research across evolutionary boundaries.

| S-EPMC2891588 | biostudies-literature

Structural basis of semaphorin-plexin cis interaction.

Project description:Semaphorin ligands interact with plexin receptors to contribute to functions in the development of myriad tissues including neurite guidance and synaptic organisation within the nervous system. Cell-attached semaphorins interact in trans with plexins on opposing cells, but also in cis on the same cell. The interplay between trans and cis interactions is crucial for the regulated development of complex neural circuitry, but the underlying molecular mechanisms are uncharacterised. We have discovered a distinct mode of interaction through which the Drosophila semaphorin Sema1b and mouse Sema6A mediate binding in cis to their cognate plexin receptors. Our high-resolution structural, biophysical and in vitro analyses demonstrate that monomeric semaphorins can mediate a distinctive plexin binding mode. These findings suggest the interplay between monomeric vs dimeric states has a hereto unappreciated role in semaphorin biology, providing a mechanism by which Sema6s may balance cis and trans functionalities.

| S-EPMC7327498 | biostudies-literature

Structural basis of Janus kinase trans-activation.

Project description:Janus kinases (JAKs) mediate signal transduction downstream of cytokine receptors. Cytokine-dependent dimerization is conveyed across the cell membrane to drive JAK dimerization, trans-phosphorylation, and activation. Activated JAKs in turn phosphorylate receptor intracellular domains (ICDs), resulting in the recruitment, phosphorylation, and activation of signal transducer and activator of transcription (STAT)-family transcription factors. The structural arrangement of a JAK1 dimer complex with IFNλR1 ICD was recently elucidated while bound by stabilizing nanobodies. While this revealed insights into the dimerization-dependent activation of JAKs and the role of oncogenic mutations in this process, the tyrosine kinase (TK) domains were separated by a distance not compatible with the trans-phosphorylation events between the TK domains. Here, we report the cryoelectron microscopy structure of a mouse JAK1 complex in a putative trans-activation state and expand these insights to other physiologically relevant JAK complexes, providing mechanistic insight into the crucial trans-activation step of JAK signaling and allosteric mechanisms of JAK inhibition.

| S-EPMC10180219 | biostudies-literature

Structural Basis of Arrestin-Dependent Signal Transduction.

Project description:Arrestins are a small family of proteins with four isoforms in humans. Remarkably, two arrestins regulate signaling from >800 G protein-coupled receptors (GPCRs) or nonreceptor activators by simultaneously binding an activator and one out of hundreds of other signaling proteins. When arrestins are bound to GPCRs or other activators, the affinity for these signaling partners changes. Thus, it is proposed that an activator alters arrestin's ability to transduce a signal. The comparison of all available arrestin structures identifies several common conformational rearrangements associated with activation. In particular, it identifies elements that are directly involved in binding to GPCRs or other activators, elements that likely engage distinct downstream effectors, and elements that likely link the activator-binding sites with the effector-binding sites.

| S-EPMC5959776 | biostudies-literature

Cis-trans

Project description:Cis-trans

| PRJEB1227 | ENA

Neuroligin-1-dependent competition regulates cortical synaptogenesis and synapse number.

Project description:Members of the neuroligin family of cell-adhesion proteins are found at excitatory and inhibitory synapses and are mutated in some familial forms of autism spectrum disorders. Although they display synaptogenic properties in heterologous systems, the function of neuroligins in vivo in the regulation of synapse formation and synapse number has been difficult to establish. We found that neuroligin-1 (NL1), which is located at excitatory postsynaptic densities, regulates activity-dependent synaptogenesis and mature synapse number on cortical layer 2/3 pyramidal neurons in vivo. However, synapse number was not sensitive to absolute NL1 levels but instead depended on transcellular differences in the relative amounts of NL1. These effects were independent of the cell-autonomous regulation of NMDA-type glutamate receptors by absolute levels of NL1. Our data indicate that transcellular competitive processes govern synapse formation and number in developing cortex and that NL1 has a central function in these processes.

| S-EPMC3536444 | biostudies-literature

Femtosecond structural dynamics drives the trans/cis isomerization in photoactive yellow protein.

Project description:A variety of organisms have evolved mechanisms to detect and respond to light, in which the response is mediated by protein structural changes after photon absorption. The initial step is often the photoisomerization of a conjugated chromophore. Isomerization occurs on ultrafast time scales and is substantially influenced by the chromophore environment. Here we identify structural changes associated with the earliest steps in the trans-to-cis isomerization of the chromophore in photoactive yellow protein. Femtosecond hard x-ray pulses emitted by the Linac Coherent Light Source were used to conduct time-resolved serial femtosecond crystallography on photoactive yellow protein microcrystals over a time range from 100 femtoseconds to 3 picoseconds to determine the structural dynamics of the photoisomerization reaction.

| S-EPMC5291079 | biostudies-literature

Cis-trans

Project description:Differential Expression analysis in Drosophila pseudoobscura to identify cis-trans regulation

2014-03-27 | E-MTAB-1424 | biostudies-arrayexpress

Structural basis of Sorcin-mediated calcium-dependent signal transduction.

Project description:Sorcin is an essential penta-EF hand calcium binding protein, able to confer the multi-drug resistance phenotype to drug-sensitive cancer cells and to reduce Endoplasmic Reticulum stress and cell death. Sorcin silencing blocks cell cycle progression in mitosis and induces cell death by triggering apoptosis. Sorcin participates in the modulation of calcium homeostasis and in calcium-dependent cell signalling in normal and cancer cells. The molecular basis of Sorcin action is yet unknown. The X-ray structures of Sorcin in the apo (apoSor) and in calcium bound form (CaSor) reveal the structural basis of Sorcin action: calcium binding to the EF1-3 hands promotes a large conformational change, involving a movement of the long D-helix joining the EF1-EF2 sub-domain to EF3 and the opening of EF1. This movement promotes the exposure of a hydrophobic pocket, which can accommodate in CaSor the portion of its N-terminal domain displaying the consensus binding motif identified by phage display experiments. This domain inhibits the interaction of sorcin with PDCD6, a protein that carries the Sorcin consensus motif, co-localizes with Sorcin in the perinuclear region of the cell and in the midbody and is involved in the onset of apoptosis.

| S-EPMC4649501 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data