iTRAQ-Based Serum Proteomic Analysis Reveals Multifactorial Cellular Function Impairment and Aggravated Systematic Inflammation in Drug-free Obsessive-Compulsive Disorders DOI
Miaohan Deng, Xia Li, Dongdong Shi

et al.

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(16), P. 3053 - 3063

Published: Aug. 9, 2024

Obsessive-compulsive disorder (OCD) is a debilitating mental with obvious difficulties in treatment. Its pathogenesis has not been fully elucidated. Further understanding of etiology and mechanism needs to be explored further. We employed the isobaric tag for relative absolute quantitation (iTRAQ)-based proteomic analysis compare serum proteome profile between OCD patients healthy controls, order find out possible downstream biological process. Eighty-one drug-free 78 controls were enrolled. A total 475 proteins identified. Totally, 80

Language: Английский

EndoMAPV1, a Structural Protein Complex Landscape of Human Endosomes DOI Creative Commons
Miguel A. Gonzalez‐Lozano, E. Schmid, Enya Miguel Whelan

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 9, 2025

ABSTRACT Early/sorting endosomes are dynamic organelles that play key roles in proteome control by triaging plasma membrane proteins for either recycling or degradation the lysosome 1,2,3 . These events coordinated numerous transiently-associated regulatory complexes and integral components contribute to organelle identity during endosome maturation 4 While a subset of several hundred protein cargoes known associate with have been studied at biochemical and/or structural level, interaction partners higher order molecular assemblies many endosomal remain unknown. Here, we combine cross-linking native gel mass spectrometry 5-8 purified early AlphaFold 9,10 computational analysis create systematic human interactome. We present dozens models pairs supported experimental cross-links from their subcellular context, suggesting mechanisms previously reported processes. Using induced neurons, validate two candidate whose interactions crosslinks predictions: TMEM230 as subunit ATP8/11 lipid flippases 11 TMEM9/9B subunits CLCN3/4/5 chloride-proton antiporters 12 This resource its accompanying network viewer provide an framework understanding organellar interactomes large-scale validation predictions.

Language: Английский

Citations

0
RIM and MUNC13 membrane–binding domains are essential for neuropeptide secretion DOI Creative Commons
Fiona H Murphy, Adlin Abramian,

Remco V. Klaassen

et al.

The Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 224(7)

Published: May 12, 2025

Neurons release neurotransmitters from synaptic vesicles (SVs) and neuropeptides dense-core (DCVs). The presynaptic proteins RIM MUNC13 play key roles in both pathways. It remains unclear how DCVs are targeted to sites whether involved this process. Here, we show that three membrane-binding domains regulate DCV exocytosis differently SV exocytosis. Using neuropeptide secretion assays with single-vesicle resolution peptidomics analysis of endogenous MUNC13/RIM null neurons, demonstrate is essential for N terminus prevents degradation via the proteasome, inhibiting proteasomal partially rescues RIM’s absence. Unlike exocytosis, PIP2-binding C2B domain C1-C2B polybasic face redundant while lipid-binding C2C crucial. These results synergistically through membrane interactions reveal new mechanistic differences between

Language: Английский

Citations

0
EndoMAP.v1 charts the structural landscape of human early endosome complexes DOI Creative Commons
Miguel A. Gonzalez‐Lozano, E. Schmid, Enya Miguel Whelan

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: May 28, 2025

Language: Английский

Citations

0
Tomosyns attenuate SNARE assembly and synaptic depression by binding to VAMP2-containing template complexes DOI Creative Commons
Marieke Meijer, Miriam Öttl, Jie Yang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 26, 2024

Abstract Tomosyns are widely thought to attenuate membrane fusion by competing with synaptobrevin-2/VAMP2 for SNARE-complex assembly. Here, we present evidence against this scenario. In a novel mouse model, tomosyn-1/2 deficiency lowered the barrier and enhanced probability that synaptic vesicles fuse, resulting in stronger synapses faster depression slower recovery. While wild-type tomosyn-1m rescued these phenotypes, substitution of its SNARE motif did not. Single-molecule force measurements indeed revealed tomosyn’s cannot substitute form template complexes Munc18-1 syntaxin-1, an essential intermediate Instead, tomosyns extensively bind synaptobrevin-2/VAMP2-containing prevent SNAP-25 association. Structure-function analyses indicate C-terminal polybasic region contributes inhibitory function. These results reveal regulate transmission cooperating binding during assembly, thereby limiting initial strength equalizing it repetitive stimulation.

Language: Английский

Citations

1
iTRAQ-Based Serum Proteomic Analysis Reveals Multifactorial Cellular Function Impairment and Aggravated Systematic Inflammation in Drug-free Obsessive-Compulsive Disorders DOI
Miaohan Deng, Xia Li, Dongdong Shi

et al.

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(16), P. 3053 - 3063

Published: Aug. 9, 2024

Obsessive-compulsive disorder (OCD) is a debilitating mental with obvious difficulties in treatment. Its pathogenesis has not been fully elucidated. Further understanding of etiology and mechanism needs to be explored further. We employed the isobaric tag for relative absolute quantitation (iTRAQ)-based proteomic analysis compare serum proteome profile between OCD patients healthy controls, order find out possible downstream biological process. Eighty-one drug-free 78 controls were enrolled. A total 475 proteins identified. Totally, 80

Language: Английский

Citations

0