Disease relevance of Syn1

• Alterations in BDNF and synapsin I within the occipital cortex and hippocampus after mild traumatic brain injury in the developing rat: reflections of injury-induced neuroplasticity [1].
• We studied brain synapsin I and II mRNA levels using the amygdala kindling model of epilepsy [2].
• Two versions of the virus were made in which EGFP expression was driven either by the Rous sarcoma virus U3 enhancer or by a combination of sequences from the Syn1 and Pgk-1 promoters [3].
• Using the cDNA encoding rat synapsin IIb, we employed an Escherichia coli expression system to synthesize a variety of fusion proteins containing a truncated protein A linked to different portions of the NH2-terminal region of synapsin II [4].
• Endurance exercise regimens induce differential effects on brain-derived neurotrophic factor, synapsin-I and insulin-like growth factor I after focal ischemia [5].

Psychiatry related information on Syn1

• Supplementation of omega-3 fatty acids in the diet counteracted all of the studied effects of FPI, that is, normalized levels of BDNF and associated synapsin I and CREB, reduced oxidative damage, and counteracted learning disability [6].

High impact information on Syn1

• Ca2+/calmodulin-dependent protein kinase II, which phosphorylates two sites in the carboxy-terminal region of synapsin I, causes synapsin I to dissociate from synaptic vesicles and increases neurotransmitter release [7].
• Synaptic vesicle-associated Ca2+/calmodulin-dependent protein kinase II is a binding protein for synapsin I [7].
• Induction of formation of presynaptic terminals in neuroblastoma cells by synapsin IIb [8].
• Synapsin I and synapsin II are neuron-specific phosphoproteins that have a role in the regulation of neurotransmitter release and in the formation of nerve terminals [9].
• These studies indicate that the rate of synapsin dispersion is controlled by phosphorylation, which in turn controls the kinetics of vesicle pool turnover [10].

Chemical compound and disease context of Syn1

• These results suggest that enhancement of BDNF and synapsin I expression by nefiracetam treatment may be, at least in part, due to the improvement in the CREB binding activity, contributing to the prevention of learning and memory dysfunction after sustained cerebral ischemia [11].
• Depolarization of spinal cord-dorsal root ganglion cocultured cells (by high K+ or veratridine) and the addition of forskolin (which activates adenylate cyclase) led to increased phosphorylation of synapsin I [12].
• The present study was undertaken to elucidate pathophysiological changes in noradrenaline release, phosphorylation of synapsin I and ultrastructure of the cerebrocortical nerve terminals following microsphere embolism in rats [13].
• To investigate the course of trans-synaptic propagation of neural activity and plasticity in temporal lobe epilepsy, time-dependent changes in the level of synapsin I, a synaptic vesicle protein that is a marker of enhanced synaptic activity and synaptogenesis, were examined following kainate-induced epileptic status in rats [14].
• Rabies virus also co-localized with synapsin I, a synaptic vesicle marker, in nerve terminals but did not co-localize with lysosomal glycoprotein [15].

Biological context of Syn1

• Like other synapsins, synapsin IIIa binds ATP with high affinity and ADP with a lower affinity, consistent with a cycle of ATP binding and hydrolysis [16].
• We observed that the majority of ERK1/2 activity induced by glucose remains in the cytoplasm and physically interacts with synapsin I, allowing phosphorylation of the substrate [17].
• Using the MIN6 beta-cell line and isolated rat islets of Langerhans, we investigated whether glucose, by activating the ERK1/2 cascade, induces phosphorylation of cytoplasmic proteins implicated in exocytosis of insulin granules such as synapsin I [17].
• These sites are flanked by three regions of repeating amino acid sequence that are proposed to be the synaptic vesicle-binding domain of synapsin I [18].
• A rat brain cDNA clone containing an open reading frame encoding the neuron-specific protein synapsin I has been sequenced [18].

Anatomical context of Syn1

• Extracellularly regulated kinases 1/2 (p44/42 mitogen-activated protein kinases) phosphorylate synapsin I and regulate insulin secretion in the MIN6 beta-cell line and islets of Langerhans [17].
• Increased PLD activity induced by PMA treatment resulted in elevated synapsin I expression and neurite outgrowth during neuronal differentiation [19].
• Expression level of synapsin I, a marker of synaptogenesis, also increased as the differentiation of neural stem cells progressed [19].
• Synaptic vesicle mobilization is regulated by distinct synapsin I phosphorylation pathways at different frequencies [20].
• During action potential firing, the rate of synapsin dissociation from synaptic vesicles and dispersion into axons controls the rate of vesicle availability for exocytosis at the plasma membrane [20].

Associations of Syn1 with chemical compounds

• Taken together, our results demonstrate new aspects of the glucose-dependent actions of ERK1/2 in beta-cells exerted on cytoplasmic proteins, including synapsin I, and participating in the overall glucose-induced insulin secretion [17].
• In a synaptosomal preparation, brain-derived neurotrophic factor (BDNF) increased mitogen-activated protein (MAP) kinase-dependent synapsin I phosphorylation and acutely facilitated evoked glutamate release [21].
• In the present study, two crystal structures of the C domain of rat synapsin I (rSynI-C) in complex with Ca(2+) and ATP reveal that this protein can form a tetramer and that a flexible loop (the "multifunctional loop") contacts bound ATP [22].
• In addition, synapsin I, phospho-synapsin I, cyclic-AMP response-element-binding protein (CREB), phospho-CREB, calcium-calmodulin-dependent protein kinase II (CAMKII), mitogen-activated protein (MAP) kinase I and II (MAPKI and MAPKII), and protein kinase C (PKC) were analyzed by western blot [23].
• Immunohistochemical detection of synapsin I and microtubule associated protein 2 revealed the synapse loss between neurons intoxicated by aluminum maltolate [24].

Physical interactions of Syn1

• Male adult rats were maintained on a HF diet for 2 months with or without 500 IU/kg of vitamin E. Supplementation of the HF diet with vitamin E dramatically reduced oxidative damage, normalized levels of BDNF, synapsin I and cyclic AMP-response element-binding protein (CREB), caused by the consumption of the HF diet [25].
• Synapsin I interacts with c-Src and stimulates its tyrosine kinase activity [26].
• Neural nitric oxide synthase (nNOS), synapsin I, and nNOS adapter protein (CAPON) constitute a ternary complex necessary for specific NO and synapsin functions at a presynaptic level [27].

Enzymatic interactions of Syn1

• FPI alone resulted in significantly elevated levels of hippocampal phosphorylated synapsin I and phosphorylated cyclic AMP response element-binding-protein (CREB) at postinjury day 7, of which phosphorylated CREB remained elevated at postinjury day 21 [28].
• A calcium/calmodulin-dependent protein kinase from mammalian brain that phosphorylates Synapsin I: partial purification and characterization [29].
• We reported previously that phosphorylated neuromodulin and phosphorylated synapsin I content increased in the striata of amphetamine-sensitized rats; however, the neuronal pathways responsible for the increase were unclear [30].

Co-localisations of Syn1

• Rab3a immunoreactivity (-IR) was always colocalized with synaptophysin-IR and synapsin I-IR in nerve terminals of the spinal cord and peripheral nerve endings [31].
• MAP-2+ neuronal soma and rapidly growing dendrites were co-localized with synapsin I puncta faithfully along DETA lines [32].

Regulatory relationships of Syn1

• Application of the mGluR antagonist (RS)-alpha-Methyl-4-carboxyphenylglycine (MCPG) blocked t-ACPD-induced inhibition of synapsin phosphorylation but not the effects of L-AP4 [33].
• Furthermore, all synapsin II+ terminals appear to be distinct from those expressing the GABA synthetic enzyme glutamic acid decarboxylase [34].
• Covalent modification of synapsin I by a tetanus toxin-activated transglutaminase [35].
• The sigma ligand 1,3-di-O-tolylguanidine (DTG) increased basal dynamin and decreased depolarization-stimulated phosphorylation of the synaptosomal protein synapsin Ib without having direct effects on protein kinases or protein phosphatases [36].

Other interactions of Syn1

• ATP binding to the different synapsins is directly regulated by Ca2+ in a dramatically different fashion: Ca2+ activates ATP binding to synapsin I, has no effect on synapsin II, and inhibits synapsin III [16].
• Synapsin III, a novel synapsin with an unusual regulation by Ca2+ [16].
• To figure out the effect of PLD on synapsin I expression, we treated the neural stem cells with phorbol myristate acetate (PMA) to stimulate PLD activity [19].
• These results indicate that exercise induces plasticity of select hippocampal transsynaptic circuitry, possibly comprising a spatial restriction on synapsin I regulation by BDNF [37].
• BDNF and synapsin I mRNAs were lower and NT-3 levels were higher in the lumbar hemicord ipsilateral to the BTX-A injection [38].

Analytical, diagnostic and therapeutic context of Syn1

• The comparative localization of two prominent synaptic proteins, synapsin-I (Syn-I) and PSD-95, was investigated in slices of developing (P3-P21) rat cerebellar cortex using double- or triple-label fluorescence immunohistochemistry and confocal microscopy [39].
• Translocational changes of localization of synapsin in axonal sprouts of regenerating rat sciatic nerves after ligation crush injury [40].
• After 5 days of treatment, cultures were analyzed for the presence of synapses by synapsin I and synaptophysin antibody labeling and by electron microscopy [41].
• Immunohistochemical studies supported the immunoblot data, showing no detectable immunofluorescence with synapsin antibodies in fetal or newborn hippocampal formation [42].
• Quantitative reverse transcriptase-polymerase chain reaction and in situ hybridization techniques were used to determine the regional distribution of synapsin IIa and IIb mRNAs in rat central nervous system and to assess the effect of chronic morphine administration on the gene expression of these two isoforms of synapsin II [43].

References