Disease relevance of Syp

• In contrast to PrP(res), caveolin 1 and synaptophysin in retina and optic nerves shifted to non-DRM fractions during the course of scrapie infection [1].
• Here we show that synaptobrevin is preferentially cleaved by tetanus toxin while bound to synaptophysin or when existing as a homodimer [2].
• The alpha-Syn(-/)- mice show no evidence of myopathy, despite reduced levels of alpha-dystrobrevin-2 [3].
• Consistent with these effects, ATPgammaS promotes phosphorylation of tyrosine receptor kinase A, early response kinase 1/2, and p38, thereby enhancing sensitivity to nerve growth factor and accelerating neurite formation in both PC12 cells and dorsal root ganglion neurons [4].
• Persistent activation of p38 mitogen-activated protein kinase in a mouse model of familial amyotrophic lateral sclerosis correlates with disease progression [5].

Psychiatry related information on Syp

• In this study, we show that Abeta reduction by active or passive Abeta immunization protects against the progressive loss of synaptophysin in the hippocampal molecular layer and frontal neocortex of a transgenic mouse model of Alzheimer's disease [6].

High impact information on Syp

• Moreover, both p38 and p38IP are required for E-cadherin downregulation during gastrulation [7].
• IRS-1 also has binding sites for Syp and Nck and other src homology 2 (SH2) signalling molecules [8].
• Regulation of gene expression by the small GTPase Rho through the ERK6 (p38 gamma) MAP kinase pathway [9].
• We now demonstrate that CTLA-4 interacts with the mu2 subunit of the plasma membrane-associated adaptor complex, AP-2, through the same motif involved in the interaction with Syp, except that the interaction with mu2 requires unphosphorylated tyrosine [10].
• CTLA-4 delivers an inhibitory signal through association of a phosphotyrosine-containing motif in the cytoplasmic domain with Syp tyrosine phosphatase [10].

Chemical compound and disease context of Syp

• AIMS/HYPOTHESIS: We investigated the effect of SB 203580, a pharmacological inhibitor of p38 mitogen-activated protein kinase (MAPK), on cardiac inflammation, cardiac fibrosis, and left ventricular function using an animal model of diabetic cardiomyopathy [11].
• This is also the first evidence that SYN, a presynaptic protein involved in neurotransmitter release, is regulated by E2 in the adult brain, and that apoE is necessary for the induction of apoJ mRNA by E2 in brain injury [12].

Biological context of Syp

• Cellugyrin represents a ubiquitously expressed four-transmembrane domain protein that is closely related to synaptic vesicle protein synaptogyrin and, more remotely, to synaptophysin [13].
• We show that in synaptosomes treated with three stimuli that induce exocytosis (a depolarizing K(+) solution, the excitatory neurotoxin alpha-latrotoxin, or the Ca(2+)-ionophore ionomycin), the homo- and heteromultimerization of synaptophysin and synaptobrevin is increased up to 6-fold [14].
• As a direct test of the requirement for IL-1 in tau phosphorylation and synaptophysin expression, IL-1 actions in neuron-microglia cocultures were manipulated [15].
• Here, we examined a role for synaptophysin in synapse formation in mixed genotype micro-island cultures of wild-type and synaptophysin-mutant hippocampal neurons [16].
• The reduced extent of synaptophysin-mutant synapse formation relative to wild-type synapses in mixed genotype cultures is attenuated by blockers of synaptic transmission [16].

Anatomical context of Syp

• We and others have thus identified a cDNA in various nonneuroendocrine cell types of rat and human that is related to synaptophysin, one of the major synaptic vesicle membrane proteins, which we termed pantophysin [17].
• Pantophysin is a ubiquitously expressed synaptophysin homologue and defines constitutive transport vesicles [17].
• Using cell fractionation in combination with immunoisolation, these vesicles are enriched in a light fraction and shown to contain the cellular vSNARE cellubrevin and the ubiquitous SCAMPs in epithelial cells and synaptophysin in neuroendocrine or cDNA-transfected nonneuroendocrine cells and neuroendocrine tissues [17].
• Upon overexpression of synaptophysin in PC12 cells, it is localized in rapidly sedimenting membranes and practically is not delivered to the SLMVs [13].
• The number of immunopositive cells in the NSE, NF, and synaptophysin staining within the infarct was progressively reduced, and after 3 to 7 days the immunoreactions were confined to discrete granulomatous structures in the center of the infarct, which otherwise was infested with macrophages [18].

Associations of Syp with chemical compounds

• Treatment with quinacrine or pentosan polysulfate cleared the PrPSc from the ScGT1-1 cell cultures, and the increase in levels of monomeric SNAP-25 and synaptophysin was reversible [19].
• Time course of response to estradiol replacement in ovariectomized mice: brain apolipoprotein E and synaptophysin transiently increase and glial fibrillary acidic protein is suppressed [20].
• The cultures were assayed for expression of several protein markers of neuronal maturity: synaptic markers (synapsin I and synaptophysin) and glutamate receptor subunits (NMDA receptor 1 and glutamate receptor 1) [21].
• To determine which tyrosine within the EpoR is responsible for binding Syp, we examined DA-3 cell lines expressing full-length mutant EpoRs bearing tyrosine to phenylalanine substitutions for each of the eight tyrosines within the intracellular domain of the EpoR [22].
• In dissociated cultures of SCG neurons, we found a significant decrease in the number of synapses with aggregates of presynaptic synaptophysin and postsynaptic neuronal acetylcholine receptor among agrin-deficient neurons as compared to wild-type neurons [23].

Physical interactions of Syp

• Synaptophysin binds to physophilin, a putative synaptic plasma membrane protein [24].
• These findings suggest a role for Rab6p in the post-Golgi transport of synaptophysin, at an early step of the biogenesis of small synaptic vesicles [25].
• Synaptophysin-containing microvesicles transport heat-shock protein hsp60 in insulin-secreting beta cells [26].

Co-localisations of Syp

• As viewed by confocal microscopy, the immunopositivity for the IFN-gamma R was co-localized with that of the presynaptic marker synaptophysin and with neuronal nitric oxide synthase in the lateral spinal nucleus, whereas only a minor overlap with these molecules was observed in laminae I and II of the dorsal horn [27].

Regulatory relationships of Syp

• IL-1 receptor antagonist (IL-1ra) as well as anti-IL-1beta antibody attenuated the influence of activated microglia on neuronal tau and synaptophysin, but anti-TNFalpha antibody was ineffective [15].
• However, phosphorylation of p38 mitogen-activated protein (MAP) kinase in Rac2(-/-) neutrophils was evident in response to CB/fMLP and/or TNF [28].
• The role of p38 mitogen-activated protein kinase in IL-1 beta transcription [29].
• Cellular stress induces the tyrosine phosphorylation of caveolin-1 (Tyr(14)) via activation of p38 mitogen-activated protein kinase and c-Src kinase. Evidence for caveolae, the actin cytoskeleton, and focal adhesions as mechanical sensors of osmotic stress [30].
• Our data indicate that HO-1 acts as a signal terminator of tumor necrosis factor alpha-induced apoptosis by modulation of the p38 mitogen-activated protein kinase pathway [31].

Other interactions of Syp

• Moreover, expression of cellugyrin (or synaptogyrin) in PC12 cells dramatically and specifically increases SLMV targeting of endogenous synaptophysin [13].
• The increase in multimerization of synaptophysin and synaptobrevin was only observed in intact but not in lysed synaptosomes and could not be inhibited by general kinase or phosphatase inhibitors [14].
• Although NACP appeared early in CNS development, synaptophysin levels started to rise at a later stage [32].
• In contrast to GFAP, synaptophysin and apoE concentrations were significantly elevated by 15% and 25%, respectively, in the E2-replaced group compared to the vehicle-replaced group at 5 days but by 14 days concentrations were equivalent [20].
• Postnatal neurons successfully survived for a long term (up to 40 days) in vitro in serum-free media, as characterized by the expression of synapsin I, synaptophysin, and microtubule-associated protein 2 [21].

Analytical, diagnostic and therapeutic context of Syp

• To understand better the patterns of NACP expression during development, we analyzed the levels of this protein as well as the levels of another synaptic protein (synaptophysin) by ribonuclease protection assay, western blotting, and immunocytochemistry in fetal, juvenile, and adult mouse brain [32].
• Immunofluorescence microscopy of several neuronal and neuroendocrine tissues showed that overall tissue architecture was maintained in the absence of synaptophysin, and that the distribution of other synaptic vesicle components was not visibly affected [33].
• The present study quantified potential synaptic plasticity throughout the brains of C57BL/6 mice using an enzyme-linked immunosorbent assay (ELISA) for two synaptic proteins, synaptophysin and PSD-95 [34].
• Electron microscopy and double immunostaining for synaptophysin and a marker of gamma-aminobutyric acid-ergic terminals documented a rich synaptic input to these neurons [35].
• Furthermore, we have established by light microscopy immunocytochemistry that this region of the calyx also contains a high concentration of synaptophysin, another well-characterized major component of small synaptic vesicle membranes [36].

References