ArticlePloS one2017
Myosin phosphatase and RhoA-activated kinase modulate neurotransmitter release by regulating SNAP-25 of SNARE complex.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.
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12 citing papers in PubMed, 19 citations in OpenAlex.
- Distinct Effects of Nonselective Rho-Kinase Inhibitor Fasudil and Selective Rho-Kinase 2 Inhibitor KD025 on Serotonin and Dopamine Release in the Nucleus Accumbens of Mice.Neuropsychopharmacology reports · 2026Article
- Research progress on the function of non-muscle myosin II during cell division.Frontiers in cell and developmental biology · 2026Review
- Phosphorylation of SNAP-25 at Ser187 is enhanced following its cleavage by Botulinum Neurotoxin Serotype A, promoting the dominant-negative effect of the resulting fragment.PLoS pathogens · 2025Article
- Myosin phosphatase targeting subunit1 controls localization and motility of Rab7-containing vesicles: Is myosin phosphatase a cytoplasmic dynein regulator?Cytoskeleton (Hoboken, N.J.) · 2024Article
- Protein phosphatase 1 regulatory inhibitor subunit 14C promotes triple-negative breast cancer progression via sustaining inactive glycogen synthase kinase 3 beta.Clinical and translational medicine · 2022Article
- TrkB signaling is correlated with muscular fatigue resistance and less vulnerability to neurodegeneration.Frontiers in molecular neuroscience · 2022Article
- Regulation of Synaptic Transmission and Plasticity by Protein Phosphatase 1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Review
- Inhibition of protein phosphatase-1 and -2A by ellagitannins: structure-inhibitory potency relationships and influences on cellular systems.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- The temporal profile of activity-dependent presynaptic phospho-signalling reveals long-lasting patterns of poststimulus regulation.PLoS biology · 2019Article
- Diverse exocytic pathways for mast cell mediators.Biochemical Society transactions · 2018Review
- MicroRNA-210-5p Contributes to Cognitive Impairment in Early Vascular Dementia Rat Model Through Targeting Snap25.Frontiers in molecular neuroscience · 2018Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reversible phosphorylation of neuronal proteins plays an important role in the regulation of neurotransmitter release. Myosin phosphatase holoenzyme (MP) consists of a protein phosphatase-1 (PP1) catalytic subunit (PP1c) and a regulatory subunit, termed myosin phosphatase targeting subunit (MYPT1). The primary function of MP is to regulate the phosphorylation level of contractile proteins; however, recent studies have shown that MP is localized to neurons, and is also involved in the mediation of neuronal processes. Our goal was to investigate the effect of RhoA-activated kinase (ROK) and MP on the phosphorylation of one potential neuronal substrate, the synaptosomal-associated protein of 25 kDa (SNAP-25). SNAP-25 is a member of the SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptor) complex, along with synaptobrevin and syntaxin, and the primary role of SNAP25 is to mediate vesicle fusion. We showed that MYPT1 interacts with SNAP-25, as revealed by immunoprecipitation and surface plasmon resonance based binding studies. Mass spectrometry analysis and in vitro phosphorylation/dephosphorylation assays demonstrated that ROK phosphorylates, while MP dephosphorylates, SNAP-25 at Thr138. Silencing MYPT1 in B50 neuroblastoma cells increased phosphorylation of SNAP-25 at Thr138. Inhibition of PP1 with tautomycetin increased, whereas inhibition of ROK by H1152, decreased the phosphorylation of SNAP-25 at Thr138 in B50 cells, in cortical synaptosomes, and in brain slices. In response to the transduction of the MP inhibitor, kinase-enhanced PP1 inhibitor (KEPI), into synaptosomes, an increase in phosphorylation of SNAP-25 and a decrease in the extent of neurotransmitter release were detected. The interaction between SNAP-25 and syntaxin increased with decreasing phosphorylation of SNAP-25 at Thr138, upon inhibition of ROK. Our data suggest that ROK/MP play a crucial role in vesicle trafficking, fusion, and neurotransmitter release by oppositely regulating the phosphorylation of SNAP-25 at Thr138.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.