Publications by authors named "Bielopolski N"
Objective: Opening of voltage-gated sodium channels is crucial for neuronal depolarization. Proper channel opening and influx of Na through the ion pore, is dependent upon binding of Na ion to a specific amino-acid motif (DEKA) within the pore. In this study we used molecular dynamic simulations, an advanced bioinformatic tool, to research the dysfunction caused by pathogenic variants in SCN1a, SCN2a and SCN8a genes.
View Article and Find Full Text PDFOlfactory associative learning in is mediated by synaptic plasticity between the Kenyon cells of the mushroom body and their output neurons. Both Kenyon cells and their inputs from projection neurons are cholinergic, yet little is known about the physiological function of muscarinic acetylcholine receptors in learning in adult flies. Here, we show that aversive olfactory learning in adult flies requires type A muscarinic acetylcholine receptors (mAChR-A), particularly in the gamma subtype of Kenyon cells.
View Article and Find Full Text PDFArticle Synopsis
- Neuronal exocytosis relies on the formation of SNARE complexes, and tomosyn plays a key role in regulating this process as a SNARE-binding protein.
- Using advanced microscopy (dSTORM), researchers discovered that tomosyn clusters near syntaxin clusters on the plasma membrane, indicating a specific organizational relationship.
- Mutations in tomosyn affect its mobility and binding to SNAP25, leading to less inhibition of exocytosis, suggesting that tomosyn's inhibitory action is primarily through its interactions with the SNARE complex involving syntaxin and SNAP25.
Article Synopsis
- Tomosyn is an R-SNARE protein that regulates exocytosis in mammals and has two paralogous genes, tomosyn-1 and -2, which create seven isoforms through alternative splicing.
- Structural analysis shows that m-tomosyn-1 has a conserved core from its yeast counterpart, Sro7, but with three extra loop domains important for its function in inhibiting secretion.
- Deletion studies reveal that specific loop regions greatly affect tomosyn's ability to inhibit secretion, and modifications like SUMO conjugation can enhance its inhibitory role without affecting its interaction with other proteins.
The protein tomosyn decreases synaptic transmission and release probability of vesicles, and is essential for modulating synaptic transmission in neurons. In this study, we provide a detailed description of the expression and localization patterns of tomosyn1 and tomosyn2 in the subareas of the mouse hippocampus. Using confocal and two-photon high-resolution microscopy we demonstrate that tomosyn colocalizes with several pre- and postsynaptic markers and is found mainly in glutamatergic synapses.
View Article and Find Full Text PDFPriming is the process by which vesicles become available for fusion at nerve terminals and is modulated by numerous proteins and second messengers. One of the prominent members of this diverse family is tomosyn. Tomosyn has been identified as a syntaxin-binding protein; it inhibits vesicle priming, but its mode of action is not fully understood.
View Article and Find Full Text PDF