Search results for "SNAr"
showing 10 items of 26 documents
β1-Integrin– and K(V)1.3 channel–dependent signaling stimulates glutamate release from Th17 cells
2020
Although the impact of Th17 cells on autoimmunity is undisputable, their pathogenic effector mechanism is still enigmatic. We discovered soluble N-ethylmaleimide–sensitive factor attachment receptor (SNARE) complex proteins in Th17 cells that enable a vesicular glutamate release pathway that induces local intracytoplasmic calcium release and subsequent damage in neurons. This pathway is glutamine dependent and triggered by binding of β1-integrin to vascular cell adhesion molecule 1 (VCAM-1) on neurons in the inflammatory context. Glutamate secretion could be blocked by inhibiting either glutaminase or K(V)1.3 channels, which are known to be linked to integrin expression and highly expressed…
A Multilevel Functional Study of aSNAP25At-Risk Variant for Bipolar Disorder and Schizophrenia
2017
The synaptosomal-associated protein SNAP25 is a key player in synaptic vesicle docking and fusion and has been associated with multiple psychiatric conditions, including schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder. We recently identified a promoter variant inSNAP25,rs6039769, that is associated with early-onset bipolar disorder and a higher gene expression level in human prefrontal cortex. In the current study, we showed that this variant was associated both in males and females with schizophrenia in two independent cohorts. We then combinedin vitroandin vivoapproaches in humans to understand the functional impact of the at-risk allele. Thus, we showedin vi…
Comprehensive analysis of expression, subcellular localization, and cognate pairing of SNARE proteins in oligodendrocytes
2009
Oligodendrocytes form the central nervous system myelin sheath by spiral wrapping of their plasma membrane around axons, necessitating a high rate of exocytic membrane addition to the growing myelin membrane. Membrane fusion is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins (SNAREs), which act by specific pairing of vesicle (R)- and target (Q)-SNAREs. To characterize oligodendroglial SNAREs and their trafficking pathways, we performed a detailed expression analysis of SNAREs in differentiating cultured oligodendrocytes and myelin and determined their subcellular localization. Expression of the plasma membrane Q-SNAREs syntaxin 3, syntaxin 4, SNAP2…
Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles.
1999
Here, to study lipid-protein interactions that contribute to the biogenesis of regulated secretory vesicles, we have developed new approaches by which to label proteins in vivo, using photoactivatable cholesterol and glycerophospholipids. We identify synaptophysin as a major specifically cholesterol-binding protein in PC12 cells and brain synaptic vesicles. Limited cholesterol depletion, which has little effect on total endocytic activity, blocks the biogenesis of synaptic-like microvesicles (SLMVs) from the plasma membrane. We propose that specific interactions between cholesterol and SLMV membrane proteins, such as synaptophysin, contribute to both the segregation of SLMV membrane constit…
Epäkerrotun mahdollisuuksia Elina Hirvosen romaanissa Että hän muistaisi saman
2012
The possibilities of the disnarrated in Elina Hirvonen’s novel When I Forgot Anna, the character-narrator of When I Forgot (2005), a debut novel by Elina Hirvonen, spends the present-day of the novel sitting in the cafes and remembering the past. She works through some traumatic events and embarrassing situations, and speculates what could have happened. Her unrealized desires, fantasies etc. constitute what Gerald Prince calls the disnarrated. As delineated by Prince, the disnarrated refers to those events that remain unrealized though they are given as possible or actual elements of the narrative. It can fulfill various functions of which the present article examines its possibilities as …
On the Nucleophilic Reactivity of 4,6-Dichloro-5-nitrobenzofuroxan with Some Aliphatic and Aromatic Amines: Selective nucleophilic substitution
2020
The reaction rates for the nucleophilic aromatic substitution of 4,6-dichloro-5-nitrobenzofuroxan 1 with eight aliphatic amines (characterized by very different basicities/ nucleophilicities) and three anilines have been measured in both methanol and toluene. The obtained rates have been related to the basicity (pKaH in water and Kb in benzene) or nucleophilicity (N Mayr constants) of the tested amines. The whole of the obtained kinetic data has furnished useful information on the high nucleophilic reactivity of benzofuroxan derivatives, which has been related essentially to two factors: the high electron-drawing ability/power of the condensed furoxan ring and the low aromatic character of …
Stx5 is a novel interactor of VLDL-R to affect its intracellular trafficking and processing
2012
We identified syntaxin 5 (Stx5), a protein involved in intracellular vesicle trafficking, as a novel interaction partner of the very low density lipoprotein (VLDL)-receptor (VLDL-R), a member of the LDL-receptor family. In addition, we investigated the effect of Stx5 on VLDL-R maturation, trafficking and processing. Here, we demonstrated mutual association of both proteins using several in vitro approaches. Furthermore, we detected a special maturation phenotype of VLDL-R resulting from Stx5 overexpression. We found that Stx5 prevented advanced Golgi-maturation of VLDL-R, but did not cause accumulation of the immature protein in ER, ER to Golgi compartments, or cis-Golgi ribbon, the main ex…
Mutations in the Neuronal Vesicular SNARE VAMP2 Affect Synaptic Membrane Fusion and Impair Human Neurodevelopment
2019
VAMP2 encodes the vesicular SNARE protein VAMP2 (also called synaptobrevin-2). Together with its partners syntaxin-1A and synaptosomal-associated protein 25 (SNAP25), VAMP2 mediates fusion of synaptic vesicles to release neurotransmitters. VAMP2 is essential for vesicular exocytosis and activity-dependent neurotransmitter release. Here, we report five heterozygous de novo mutations in VAMP2 in unrelated individuals presenting with a neurodevelopmental disorder characterized by axial hypotonia (which had been present since birth), intellectual disability, and autistic features. In total, we identified two single-amino-acid deletions and three non-synonymous variants affecting conserved resid…
Transport of the major myelin proteolipid protein is directed by VAMP3 and VAMP7.
2011
CNS myelination by oligodendrocytes requires directed transport of myelin membrane components and a timely and spatially controlled membrane expansion. In this study, we show the functional involvement of the R-solubleN-ethylmaleimide-sensitive factor attachment protein receptor (R-SNARE) proteins VAMP3/cellubrevin and VAMP7/TI-VAMP in myelin membrane trafficking. VAMP3 and VAMP7 colocalize with the major myelin proteolipid protein (PLP) in recycling endosomes and late endosomes/lysosomes, respectively. Interference with VAMP3 or VAMP7 function using small interfering RNA-mediated silencing and exogenous expression of dominant-negative proteins diminished transport of PLP to the oligodendro…
Identification of SNARE complex modulators that inhibit exocytosis from an alpha-helix-constrained combinatorial library.
2003
Synthetic peptides patterned after the proteins involved in vesicle fusion [the so-called SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) proteins] are potent inhibitors of SNARE complex assembly and neuronal exocytosis. It is noteworthy that the identification of peptide sequences not related to the SNARE proteins has not been accomplished yet; this is due, in part, to the structural constraints and the specificity of the protein interactions that govern the formation of the SNARE complex. Here we have addressed this question and used a combinatorial approach to identify peptides that modulate the assembly of the SNARE core complex and inhibit neuronal…