Structure of synaptogyrin (p29) defines novel synaptic vesicle protein.

Stenius, Katinka; Janz, Roger; Südhof, Thomas C.; Jahn, Reinhard

doi:10.1083/jcb.131.6.1801

Cited by 81 publications

(79 citation statements)

References 55 publications

(71 reference statements)

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“…The topology of rat synaptogyrin suggests that the N terminus, C terminus, and the small loop between the second and the third transmembrane domain of SNG-1 reside in the cytoplasm (Stenius et al, 1995; Nonet, 1999). Reasoning that the localization of SNG-1 might be mediated by interactions with cytoplasmic factors, we deleted cytoplasmic domains of SNG-1 and assessed the ability of the lesioned proteins to localize in vivo ( Figure 4C).…”

Section: A Synaptic Localization Signal Resides In Cterminal Domain Omentioning

confidence: 99%

“…Moreover, both synaptogyrin and synaptophysin families contain nonneuronal isoforms that are ubiquitously expressed (Haass et al, 1996;Janz and Sü dhof, 1998;Kedra et al, 1998;Takeshima et al, 1998). Synaptophysin and synaptogyrin share similar membrane topologies with four transmembrane domains where their N and C termini face the cytoplasm (Johnston et al, 1989;Stenius et al, 1995). In PC12 cells, overexpressing synaptogyrin and synaptophysin inhibits exocytosis (Sugita et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…In this study we have characterized signals required for localization of members of the synaptogyrin family, which currently consists of three human genes, three mouse genes, two rat genes and one C. elegans gene (Stenius et al, 1995;Janz and Sü dhof, 1998;Kedra et al, 1998;Nonet et al, 1999). The first cloned member of this family, rat synaptogyrin (p29), is highly expressed in neurons and neuroendocrine cells where it colocalizes with synaptophysin on SVs and SLMVs (Baumert et al, 1990;Stenius et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

“…The first cloned member of this family, rat synaptogyrin (p29), is highly expressed in neurons and neuroendocrine cells where it colocalizes with synaptophysin on SVs and SLMVs (Baumert et al, 1990;Stenius et al, 1995). Synaptogyrin together with synaptophysin, a family distantly related to synaptogyrin, accounts for Ͼ10% of the total SV protein content (Jahn et al, 1985;Wiedenmann and Franke, 1985;Baumert et al, 1990;Jahn and Sü dhof, 1993;Stenius et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

“…Qualitative and quantitative analysis of the distribution of GFP-tagged protein in live animals under fluorescent microscopy is simple owing to the transparent nature of the organism (Labrousse et al, 1998; Nonet, 1999). Finally, genes that are involved in protein localization can be isolated in classical genetic screens with the use of GFPtagged transgenes (reviewed by Koushika and Nonet, 2000).In this study we have characterized signals required for localization of members of the synaptogyrin family, which currently consists of three human genes, three mouse genes, two rat genes and one C. elegans gene (Stenius et al, 1995;Janz and Sü dhof, 1998;Kedra et al, 1998; Nonet et al, 1999). The first cloned member of this family, rat synaptogyrin (p29), is highly expressed in neurons and neuroendocrine cells where it colocalizes with synaptophysin on SVs and SLMVs (Baumert et al, 1990;Stenius et al, 1995).…”

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A Conserved Mechanism of Synaptogyrin Localization

Zhao

Nonet

2001

MBoC

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We have studied the localization of synaptogyrin family members in vivo. Both native and green fluorescent protein (GFP)-tagged Caenorhabditis elegans synaptogyrin (SNG-1) are expressed in neurons and synaptically localized. Deletion and mutational analysis with the use of GFP-tagged SNG-1 has defined a 38 amino acid sequence within the C terminus of SNG-1 and a single arginine in the cytoplasmic loop between transmembrane domain 2 and 3 that are required for SNG-1 localization. These domains may represent components of signals that target synaptogyrin for endocytosis from the plasma membrane and direct synaptogyrin to synaptic vesicles, respectively. In chimeric studies, these regions were sufficient to relocalize cellugyrin, a nonneuronal form of synaptogyrin, from nonsynaptic regions such as the sensory dendrites and the cell body to synaptic vesicles. Furthermore, GFP-tagged rat synaptogyrin is synaptically localized in neurons of C. elegans and in cultured hippocampal neurons. Similarly, the C-terminal domain of rat synaptogyrin is necessary for localization in hippocampal neurons. Our study suggests that the mechanisms for synaptogyrin localization are likely to be conserved from C. elegans to vertebrates. INTRODUCTIONSynaptic vesicles (SVs) contain a restricted set of membrane proteins important for neuronal function (Sü dhof, 1995;Calakos and Scheller, 1996;Fernandez-Chacon and Sü dhof, 1999). The mechanisms responsible for targeting these proteins specifically to the SV membrane are poorly understood. Integral membrane proteins are synthesized on the rough endoplasmic reticulum and traffic through the Golgi network. Proteins exiting the trans-Golgi network (TGN) are sorted to different types of transport vesicles. SV proteins are sorted to synaptic vesicle precursors (preSVs), which differ from mature SVs both in morphology and protein composition (Tsukita and Ishikawa, 1980; Okada et al., 1995). Evidence supports both direct routing of SV proteins from TGN to preSVs and indirect routing via the plasma membrane (reviewed by Hannah et al., 1999). preSVs are subsequently transported along axonal processes to the nerve terminal by motor proteins of the kinesin superfamily (reviewed by Hirokawa, 1998). How preSVs mature after delivery to the nerve terminal is unknown. preSVs might fuse with an endosomal compartment and SVs generated by budding from the endosome. A second, but not mutually exclusive possibility, is that preSVs are delivered to the presynaptic plasma membrane at the nerve terminal and then retrieved by the same mechanism(s) used to recycle SVs after regulated exocytosis (Hannah et al., 1999; reviewed by Buckley et al., 2000). Regardless of the exact route of trafficking to the mature organelle, SV proteins must be sorted away from other membrane proteins at several stages during their life cycle.Signal sequences resident in proteins are thought to mediate the sorting of many proteins to cellular compartments. Several studies have identified domains and motifs necessary for correct localizati...

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Section: A Synaptic Localization Signal Resides In Cterminal Domain Omentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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A Conserved Mechanism of Synaptogyrin Localization

Zhao

Nonet

2001

MBoC

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Identification of yeast deletion strains that are hypersensitive to brefeldin A or monensin, two drugs that affect intracellular transport

Murén

Öyen

Barmark

et al. 2000

Yeast

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We have screened the Eurofan deletion strain collection for mutants that are either sensitive or resistant to three drugs known to affect intracellular transport: brefeldin A, monensin and C2‐ceramide. Drug‐sensitive mutants were analysed by complementation with cognate clones and tetrad analysis to confirm that the phenotypes are linked to the deletions. Out of 620 deletion strains, we found 18 mutants that were sensitive to either brefeldin A, monensin or both. Several of these mutants are deleted for genes that are known to be involved in intracellular transport, membrane biogenesis and/or cell wall biosynthesis. Among such previously known genes were VAM6, VAC7, SYS1, TLG2, RCY1, ERG4, ALG9 and ALG12. Some other genes recovered in our screen were not previously implicated in intracellular transport, but are related to other yeast genes with such a function. Still other genes encode proteins with no obvious link to intracellular transport. Several of these are putative transcription factors or RNA‐binding proteins, which suggests that they may affect drug sensitivity by modulating the expression of other genes or proteins. Copyright © 2000 John Wiley & Sons, Ltd.

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Characterization of synaptogyrin 3 as a new synaptic vesicle protein

Belizaire

Komanduri

Wooten

et al. 2004

J of Comparative Neurology

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Synaptogyrins comprise a family of tyrosine-phosphorylated proteins with two neuronal (synaptogyrins 1 and 3) and one ubiquitous (cellugyrin) isoform. Previous studies have indicated that synaptogyrins are involved in the regulation of neurotransmitter release. Synaptogyrin 1 is a synaptic vesicle protein; cellugyrin, by contrast, is absent from synaptic vesicles. In an effort to further characterize the synaptogyrin family, we studied the distribution of the synaptogyrin 3 protein in the nervous system. Subcellular fractionation and immunoprecipitation of synaptic vesicles from mouse brain showed that synaptogyrin 3 is associated with synaptic vesicles and that synaptogyrins 1 and 3 can reside on the same synaptic vesicle. Immunofluorescent staining of cultured hippocampal neurons confirmed the synaptic localization of synaptogyrin 3. Analysis of the relative distributions of synaptogyrins 1 and 3 in mouse brain revealed a more restricted expression pattern for synaptogyrin 3 compared to the ubiquitous distribution of synaptogyrin 1. Strong synaptogyrin 3 labeling was observed in the mossy fiber region of the hippocampus, substantia nigra pars reticulata, pallidum, and deep cerebellar nuclei. By comparison, the striatum and reticular and ventral posterolateral thalamic nuclei, which all showed synaptogyrin 1 labeling, contained significantly less synaptogyrin 3. Finally, we used in situ hybridization experiments to correlate synaptogyrin 3 mRNA in cell bodies with synaptogyrin 3 protein at synapses. Altogether, our data indicate that neuronal synaptogyrins are differentially expressed protein isoforms that may represent functionally distinct populations of synapses and/or synaptic vesicles.

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Structure of synaptogyrin (p29) defines novel synaptic vesicle protein.

Cited by 81 publications

References 55 publications

A Conserved Mechanism of Synaptogyrin Localization

A Conserved Mechanism of Synaptogyrin Localization

Identification of yeast deletion strains that are hypersensitive to brefeldin A or monensin, two drugs that affect intracellular transport

Characterization of synaptogyrin 3 as a new synaptic vesicle protein

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