α-Synuclein (αSYN), a pivotal synaptic protein implicated in synucleinopathies such as Parkinson's disease and Lewy body dementia, undergoes protein phase separation. We reveal that vesicle-associated membrane protein 2 (VAMP2) orchestrates αSYN phase separation both in vitro and in cells. Electrostatic interactions, specifically mediated by VAMP2 via its juxtamembrane domain and the αSYN C-terminal region, drive phase separation. Condensate formation is specific for R-SNARE VAMP2 and dependent on αSYN lipid membrane binding. Our results delineate a regulatory mechanism for αSYN phase separation in cells. Furthermore, we show that αSYN condensates sequester vesicles and attract complexin-1 and -2, thus supporting a role in synaptic physiology and pathophysiology.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11322000 | PMC |
| http://dx.doi.org/10.1038/s41556-024-01451-6 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Preparation and characterization of PEG-Dex macromolecular schiff base particles and their application on the stabilization of water-in-water emulsion.
Sci Rep
December 2024
Gansu Provincial Ecological Environment Engineering Assessment Center, Lanzhou, 730000, People's Republic of China.
In this study, polyethylene glycol (PEG) and dextran (Dex) were chemically modified to obtain amino-functionalized PEG (PEG-(NH)) and oxidized dextran (ODex). They were subsequently reacted via -NH and -CHO groups to synthesize a macromolecular Schiff base particle. The structures, morphologies, and thermal properties of the macromolecular Schiff base particle were characterized using Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and thermogravimetry analysis (TGA).
View Article and Find Full Text PDFHighly Sensitive LC-MS/MS Method for Determination of Dexamethasone in Rat Plasma and Brain Tissue: An Application to Pharmacokinetic Study in Rats.
Biomed Chromatogr
January 2025
Drug Metabolism and Pharmacokinetics, Laxai Life Sciences Pvt. Ltd, Hyderabad, India.
A highly sensitive and rapid LC-MS/MS method was developed and validated for the quantification of dexamethasone in rat plasma and brain tissue. Protein precipitation method was used for sample preparation. The separation of dexamethasone and the IS (labetalol) was achieved on an Atlantis dC column using an isocratic mobile phase (10 mM ammonium formate and acetonitrile, 25/75, v/v) delivered at 0.
View Article and Find Full Text PDFSimultaneous Determination of Vitamins A and E and Their Generated Metabolites in Human Serum by LC-MS/MS.
Biomed Chromatogr
January 2025
Beijing Harmony Health Medical Diagnostics Co., Ltd., Beijing, China.
In the context of personalized and precision medicine, simultaneous monitoring of different forms of vitamins A and E and their metabolites could help us better understand the status of vitamins A and E in the body. The aim of this study was to establish a method for simultaneous determination of 13 kinds of vitamins A and E and their metabolites in human serum. Serum samples were directly detected by LC-MS/MS after deproteinization.
View Article and Find Full Text PDFMitigation of irreversible membrane biofouling by CNTs-PVDF conductive composite membrane.
Environ Res
December 2024
School of Environmental Science and Engineering, Tiangong University, State Key Laboratory of Separation Membranes and Membrane Processes, Binshui West Road 399, Xiqing District, Tianjin, 300387, PR China; Cangzhou Institute of Tiangong University, Cangzhou 061000, China. Electronic address:
Biofouling has been one of the major challenges impacting the long-term stable operation of ultrafiltration processes. Irreversible biofouling is considerably more harmful than reversible biofouling. Conductive membrane, as a new technology to effectively mitigate membrane fouling, lack research of controlling irreversible biofouling.
View Article and Find Full Text PDFLong-acting injectable in situ forming implants: Impact of polymer attributes and API.
Int J Pharm
December 2024
Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA. Electronic address:
Poly(DL-lactide-co-glycolide) (PLGA) and N-methyl-2-pyrrolidone (NMP)-based in situ forming implants are liquid formulations that solidify through phase separation following injection into the body. Drug is dissolved or suspended in the final formulation liquid prior to injection. Depending on the polymers used, the depots formed can deliver drug over different periods of time.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!