Role of Munc18-1 in the biological functions and pathogenesis of neurological disorders (Review)

Tang, Fajuan; Xiao, Dongqiong; Chen, Lin; Hu, Gao; Li, Xihong

doi:10.3892/mmr.2021.11837

Cited by 9 publications

(7 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We note that +K1431M mice exhibit reductions and +/M2145T mice exhibit increases of Stx1a and Munc18-1. Given their crucial roles in SV recycling, priming, and docking (122)(123)(124)(125), these changes may underlie the deficits and enhancements in Pr and SV pool in +K1431M and +/M2145T mice, respectively.…”

Section: Effect Of Trio Variants On Dendritesmentioning

confidence: 99%

Heterozygosity for neurodevelopmental disorder-associatedTRIOvariants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice

Ishchenko,

Jeng,

Feng

et al. 2024

Preprint

View full text Add to dashboard Cite

Heterozygosity for rare genetic variants inTRIOis associated with neurodevelopmental disorders (NDDs) including schizophrenia (SCZ), autism spectrum disorder (ASD) and intellectual disability. TRIO uses its two guanine nucleotide exchange factor (GEF) domains to activate GTPases (GEF1: Rac1 and RhoG; GEF2: RhoA) that control neuronal migration, synapse development and function. It remains unclear whether and how discreteTRIOvariants differentially impact these neurodevelopmental events. Here, we elucidate how heterozygosity for NDD-associatedTriovariants –+/K1431M(ASD),+/K1918X(SCZ), and+/M2145T(bipolar disorder, BPD) – impact mouse behavior, brain development, and synapse structure and function. Heterozygosity for differentTriovariants impacts motor, social, and cognitive behaviors in distinct ways that align with clinical phenotypes in humans. ASD- and SCZ-linkedTriovariants differentially impact head and brain size with corresponding changes in dendritic arbors of motor cortex layer 5 pyramidal neurons (M1 L5 PNs). Although dendritic spine density and synaptic ultrastructure were only modestly altered in theTriovariant heterozygotes, we observe significant changes in synaptic function and plasticity including excitatory/inhibitory imbalance and long-term potentiation defects. We also identify distinct changes in glutamate synaptic release in+/K1431Mand+/M2145Tcortico-cortical synapses, associated with deficiencies in crucial presynaptic release regulators. WhileTRIO K1431Mhas impaired ability to promote GTP exchange on Rac1,+/K1431Mmice exhibit increased Rac1 activity, suggesting possible compensation by other GEFs. Our work reveals that discrete disease-associatedTriovariants yield overlapping but distinct NDD-associated phenotypes in mice and demonstrates, for the first time, an essential role for Trio in presynaptic glutamate release, underscoring the importance of studying the impact of variant heterozygosity in vivo.

show abstract

Section: Effect Of Trio Variants On Dendritesmentioning

confidence: 99%

Heterozygosity for neurodevelopmental disorder-associatedTRIOvariants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice

Ishchenko,

Jeng,

Feng

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Any decrease in Munc production in the cells results in decreased insulin secretion. [ 17 , 21 , 22 ]…”

Section: Metabolomics In Insulin Secretion and Effectmentioning

confidence: 99%

Diabetes and diabesity in the view of proteomics, drug, and plant-derived remedies

Haeri

2023

J Res Med Sci

View full text Add to dashboard Cite

Diabetes and obesity are highly prevalent in the world. Proteomics is a promising approach to better understanding enzymes, proteins, and signaling molecules involved in diabetes processes which help recognize the basis of the disease better and find suitable new treatments. This study aimed to summarize the molecular mechanisms from the beginning of insulin secretion in response to stimuli to the pathology of the insulin signaling pathway and, finally, the mechanisms of drugs/chemicals remedies that affect this process. The titles and subtitles of this process were determined, and then for each of them, the articles searched in PubMed and ScienceDirect were used. This review article starts the discussion with the molecular basis of insulin biosynthesis, secretion, insulin’s mechanism of action, and molecular aspect of diabetes and diabesity (a new term showing the relation between diabetes and obesity) and ends with the drug and plant-derived intervention for hyperglycemia.

show abstract

“…STXBP1 (Syntaxin binding protein 1) is an evolutionarily conserved protein, which plays a key role in the release of presynaptic vesicles and neurotransmitters by interplay with syntaxin (a transmembrane attachment protein receptor) [1][2][3]. Mutations in STXBP1 are generally responsible for early infantile epileptic encephalopathy type 4 (EIEE4, OMIM # 612164) that is now collectively called STXBP1 encephalopathy (STXBP1-E).…”

Section: Introductionmentioning

confidence: 99%

A novel de novo splicing mutation of STXBP1 in epileptic encephalopathy associated with hypomyelinating leukodystrophy

Wang

Zhang

Zhou

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Deleterious variations in STXBP1 are responsible for early infantile epileptic encephalopathy type 4 (EIEE4, OMIM # 612164) because of its dysfunction in the central nervous system. The clinical spectrum of the neurodevelopmental delays associated with STXBP1 aberrations is collectively defined as STXBP1 encephalopathy (STXBP1-E), the conspicuous features of which are highlighted by early-onset epileptic seizures without structural brain anomalies. The girl first diagnosed with the unexplained disorders of movement and cognitive later was developed into STXBP1-E with unexpected leukoaraiosis and late-onset of seizures. Methods: The genetic screening and molecular tricks including trio Whole Exome Sequencing (WES), Sanger sequencing, bioengineering with CRISPR/Cas9, Western blot, qPCR/RT-PCR and bioinformatic analyses alongside neurological examinations were employed to investigate the genetic etiology and established the diagnosis. Results: A novel de novo heterozygous mutation of c.37+2dupT at STXBP1 splice site was identified as the pathogenic cause in the affected girl. The de novo mutation (DNM) didn't result in any truncated proteins, but immediately trigger mRNA degradation by nonsense-mediated mRNA decay (NMD), which led to the haploinsufficiency of STXBP1. The patient showed the atypical phenotypes characterized by hypomyelinating leukodystrophy and late-onset of epileptic seizures, which had never previously been delineated in STXBP1-E. Conclusion: The findings strongly implicated that the haploinsufficiency of STXBP1 could also exhibit divergent clinical phenotypes because of the genetic heterogeneity in the subset of encephalopathies.

show abstract

Role of Munc18-1 in the biological functions and pathogenesis of neurological disorders (Review)

Cited by 9 publications

References 71 publications

Heterozygosity for neurodevelopmental disorder-associatedTRIOvariants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice

Heterozygosity for neurodevelopmental disorder-associatedTRIOvariants yields distinct deficits in behavior, neuronal development, and synaptic transmission in mice

Diabetes and diabesity in the view of proteomics, drug, and plant-derived remedies

A novel de novo splicing mutation of STXBP1 in epileptic encephalopathy associated with hypomyelinating leukodystrophy

Contact Info

Product

Resources

About