Disease relevance of Syn1

• This may explain, at least in part, the epileptic seizures occurring in the synapsin I mutant mice [1].
• Cloning from insulinoma cells of synapsin I associated with insulin secretory granules [2].
• Using the ELISA, neither synapsin I nor synaptophysin could be determined in serum or cerebrospinal fluid (CSF) from healthy donors or patients suffering various neurological disorders or pheochromocytomas [3].
• Synaptophysin and synapsin I, another synaptic vesicle protein, are also expressed by retinoic acid-induced neuronally differentiated P19 teratocarcinoma cells [4].
• Hypoxia alone in the absence of ischemia was associated with a transient but modest increase in GLUT-3 and synapsin I protein concentrations, which did not cause significant apoptosis and/or necrosis [5].

Psychiatry related information on Syn1

• Abnormal phosphorylation of synapsin I predicts a neuronal transmission impairment in the R6/2 Huntington's disease transgenic mice [6].

High impact information on Syn1

• Wnt-7a mutant mice show a delay in the morphological maturation of glomerular rosettes and in the accumulation of synapsin I [7].
• Synapsin I, the major phosphoprotein of synaptic vesicles, is thought to play a central role in neurotransmitter release [8].
• Electrophysiology reveals that mice lacking synapsin I exhibit a selective increase in paired pulse facilitation, with no major alterations in other synaptic parameters such as long-term potentiation [8].
• Studies of knockout mice have shown that the synaptic vesicle protein Rab3A is required for mossy fibre LTP, but the protein kinase A substrates rabphilin, synapsin I and synapsin II are dispensable [9].
• Introduction of a Synapsin I promoter driven Cre transgenic mouse strain into the conditional NF1 background has ablated NF1 function in most differentiated neuronal populations [10].

Biological context of Syn1

• A GFP transgene has been integrated on the proximal part of the mouse X chromosome just distal of Timp and Syn1 [11].
• The phenotype of the synapsin knockouts could be explained either by deficient recruitment of synaptic vesicles to the active zone, or by impaired maturation of vesicles at the active zone, both of which could lead to a secondary destabilization of synaptic vesicles [12].
• Transfection experiments using synapsin II-luciferase fusion genes demonstrate that the 5'-flanking sequence functions as a strong promoter in neuronal but not in nonneuronal cells [13].
• Although there is no extensive sequence homology between the 5'-flanking regions of the synapsin I and II genes, comparison analysis has identified two regions of homologous sequences, which may be involved in determining neuron specificity of the core promoters of these two genes [13].
• To gain further insight into the functional significance of the phosphorylation sites on the synapsins, we have examined a number of synaptic processes thought to be mediated by protein kinases in knockout mice lacking both forms of synapsin (Rosahl et al., 1995) [14].

Anatomical context of Syn1

• Here, we show that synapsin I, a synaptic vesicle-associated protein, can be purified from Torpedo cholinergic synaptosomes through its affinity to cyclophilin B, an immunophilin that is particularly abundant in brain [15].
• Synapsin I deficiency results in the structural change in the presynaptic terminals in the murine nervous system [16].
• To investigate its role in the adult central nervous system, constitutively activated V12-Ha-Ras was expressed selectively in neurons of transgenic mice via a synapsin promoter [17].
• Deletion of the synapsin I genes, encoding one of the major groups of proteins on synaptic vesicles, in mice causes late onset epileptic seizures and enhanced experimental temporal lobe epilepsy [1].
• Release of glutamate from nerve endings, induced by K+,4-aminopyridine, or a Ca2+ ionophore, was markedly decreased in synapsin I mutant mice [18].

Associations of Syn1 with chemical compounds

• Synapsin associates with cyclophilin B in an ATP- and cyclosporin A-dependent manner [15].
• The effect of synapsin deletions was occluded by intracellular application of the Ca2+-chelator EGTA or of a calmodulin inhibitor [19].
• Functional studies on synaptic vesicles showed that the vesicular uptake of glutamate and GABA was decreased by 41 and 23%, respectively, while uptake of dopamine was unaffected by the lack of synapsin I and II [20].
• The formation of functional NMDA receptors also coincided with the appearance of synapsin I and synaptophysin [21].
• Decrease in phorbol ester-induced potentiation of noradrenaline release in synapsin I-deficient mice [22].

Physical interactions of Syn1

• Using a complementary approach, we confirmed an association of synapsin with NFs by demonstrating that immunoprecipitated synapsin I complexes contained NF-H and NF medium (160-kDa) subunits [23].
• Neither amelin nor synapsin I binds calmodulin, as determined by a blot binding assay [24].

Enzymatic interactions of Syn1

• Phospho-specific anti-synapsin antibodies were used to determine the distributions of site-1 phosphorylated and dephosphorylated synapsin protein [25].
• In addition, Cdk5 phosphorylates munc-18 and synapsin I, two essential components of the exocytotic machinery [26].
• Immunoblot analysis with an antibody against synapsin I phosphorylated by CaM kinase II demonstrated that treatment with tolbutamide and glucose rapidly increased phosphorylation of synapsin I and that phosphorylation was potentiated by overexpression of the isoforms [27].

Co-localisations of Syn1

• Furthermore, cyclophilin B co-localizes with synapsin I in rat synaptic vesicle fractions and its levels in synaptic vesicle-containing fractions are decreased in synapsin knockout mice [15].
• Double-labelling studies showed that VGLUT1 and VGLUT2 colocalized fully with synapsin I and/or II in the hippocampus and neostriatum, respectively [20].

Regulatory relationships of Syn1

• Inhibition of GSK-3beta by high concentrations of lithium has been shown to mimic WNT-7a signaling by inducing axonal remodeling and clustering of synapsin I in developing neurons [28].
• We suggest that CaM kinase II regulates insulin secretion via phosphorylation of synapsin I-like protein [29].

Other interactions of Syn1

• To analyse the functions of these proteins, we have studied knockout mice lacking either synapsin I, synapsin II, or both [12].
• We have investigated the developmental expression and subcellular localization of synapsin III, the newest member of the synapsin family, in cultured mouse hippocampal neurons [30].
• Consistent with our physiological evidence for synapse formation, intense punctate staining was observed with antibodies to the synaptic vesicle proteins synapsin, SV2, and synaptophysin [31].
• By analogy concerning regulation of neurotransmitter release, our results suggest that phosphorylation of synapsin I by CaM kinase II may induce the release of insulin from islet cells [2].
• As both synapsin Ib and Grb2 are implicated in neuronal signaling processes, our findings further strengthen the putative role of the prion protein in signal transduction [32].

Analytical, diagnostic and therapeutic context of Syn1

• Here, using the optical tracer FM 1-43, we characterize the details of synaptic vesicle recycling at individual synaptic boutons in hippocampal cell cultures derived from mice lacking synapsin I or wild-type equivalents [33].
• To better define the role of synapsin I in vivo, we used gene targeting to disrupt the murine synapsin I gene [16].
• Finally, synapsin I-deficient mice exhibited a strikingly increased response to electrical stimulation, as measured by electrographic and behavioral seizures [18].
• Synapsin I was expressed in normal rat islets, as determined by reverse transcriptase-polymerase chain reaction analysis [2].
• The distributions of the two synaptic vesicle proteins p65 [Matthew et al. (1981) J. Cell Biol., 91:257-269] and synapsin I [De Camilli et al. (1983) J. Cell Biol., 96:1337-1354] were compared in macaque monkey retina using pre-embedding immunocytochemistry for both light and electron microscopy [34].

References