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Journal ArticleDOI

Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal

01 Aug 1988-The Journal of Neuroscience (Society for Neuroscience)-Vol. 8, Iss: 8, pp 2804-2815
TL;DR: An antiserum against purified cholinergic synaptic vesicles from Torpedo and expression screening was used to isolate a cDNA clone encoding synuclein, a 143 amino acid neuron-specific protein that is expressed only in nervous system tissue.
Abstract: We used an antiserum against purified cholinergic synaptic vesicles from Torpedo and expression screening to isolate a cDNA clone encoding synuclein, a 143 amino acid neuron-specific protein. A cDNA clone was also isolated from a rat brain cDNA library that encodes a highly homologous 140 amino acid protein. The amino terminal 100 amino acids of both proteins are comprised of an 11 amino acid repeating unit that contains a conserved core of 6 residues. The synuclein gene is expressed only in nervous system tissue, not in electric organ, muscle, liver, spleen, heart, or kidney. In the electric organ synapse Torpedo synuclein-immunoreactive proteins are found in 3 major molecular-weight classes of 17.5, 18.5, and 20.0 kDa. In the neuronal cell soma the 17.5 kDa species is predominant and immunoreactivity is localized to a portion of the nuclear envelope.
Citations
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Journal ArticleDOI
27 Jun 1997-Science
TL;DR: A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype.
Abstract: Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromosome 4. A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype. This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder.

7,387 citations

Journal ArticleDOI
11 Sep 2003-Neuron
TL;DR: PD models based on the manipulation of PD genes should prove valuable in elucidating important aspects of the disease, such as selective vulnerability of substantia nigra dopaminergic neurons to the degenerative process.

4,872 citations


Cites background from "Synuclein: a neuron-specific protei..."

  • ...…with this view and the association of -synuclein with synaptic vesicles,presynaptic nerve terminals in close association with synaptic vesicles (Maroteaux et al., 1988; George et al., protofibrils may cause toxicity by permeabilizing synaptic vesicles (Volles et al., 2001; Lashuel et al.,…...

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Journal ArticleDOI
01 Jan 2000-Neuron
TL;DR: The hypothesis that alpha-Syn is an essential presynaptic, activity-dependent negative regulator of DA neurotransmission is supported.

1,593 citations


Cites background from "Synuclein: a neuron-specific protei..."

  • ...Two indepengic nerve terminals of the Torpedo ray electric organ dent pathological mutations have been described, a (Maroteaux et al., 1988)....

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Journal ArticleDOI
03 Nov 2000-Science
TL;DR: The selective and specific nitration of alpha-synuclein in these disorders provides evidence to directly link oxidative and nitrative damage to the onset and progression of neurodegenerative synucleinopathies.
Abstract: Aggregated α-synuclein proteins form brain lesions that are hallmarks of neurodegenerative synucleinopathies, and oxidative stress has been implicated in the pathogenesis of some of these disorders. Using antibodies to specific nitrated tyrosine residues in α-synuclein, we demonstrate extensive and widespread accumulations of nitrated α-synuclein in the signature inclusions of Parkinson's disease, dementia with Lewy bodies, the Lewy body variant of Alzheimer's disease, and multiple system atrophy brains. We also show that nitrated α-synuclein is present in the major filamentous building blocks of these inclusions, as well as in the insoluble fractions of affected brain regions of synucleinopathies. The selective and specific nitration of α-synuclein in these disorders provides evidence to directly link oxidative and nitrative damage to the onset and progression of neurodegenerative synucleinopathies.

1,553 citations

Journal ArticleDOI
TL;DR: It is reported that α-synuclein binds to small unilamellarospholipid vesicles containing acidic phospholipids, but not to vesicular charges with a net neutral charge, consistent with a role in vesicle function at the presynaptic terminal.

1,511 citations

References
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Book
15 Jan 2001
TL;DR: Molecular Cloning has served as the foundation of technical expertise in labs worldwide for 30 years as mentioned in this paper and has been so popular, or so influential, that no other manual has been more widely used and influential.
Abstract: Molecular Cloning has served as the foundation of technical expertise in labs worldwide for 30 years. No other manual has been so popular, or so influential. Molecular Cloning, Fourth Edition, by the celebrated founding author Joe Sambrook and new co-author, the distinguished HHMI investigator Michael Green, preserves the highly praised detail and clarity of previous editions and includes specific chapters and protocols commissioned for the book from expert practitioners at Yale, U Mass, Rockefeller University, Texas Tech, Cold Spring Harbor Laboratory, Washington University, and other leading institutions. The theoretical and historical underpinnings of techniques are prominent features of the presentation throughout, information that does much to help trouble-shoot experimental problems. For the fourth edition of this classic work, the content has been entirely recast to include nucleic-acid based methods selected as the most widely used and valuable in molecular and cellular biology laboratories. Core chapters from the third edition have been revised to feature current strategies and approaches to the preparation and cloning of nucleic acids, gene transfer, and expression analysis. They are augmented by 12 new chapters which show how DNA, RNA, and proteins should be prepared, evaluated, and manipulated, and how data generation and analysis can be handled. The new content includes methods for studying interactions between cellular components, such as microarrays, next-generation sequencing technologies, RNA interference, and epigenetic analysis using DNA methylation techniques and chromatin immunoprecipitation. To make sense of the wealth of data produced by these techniques, a bioinformatics chapter describes the use of analytical tools for comparing sequences of genes and proteins and identifying common expression patterns among sets of genes. Building on thirty years of trust, reliability, and authority, the fourth edition of Mol

215,169 citations

Journal ArticleDOI
TL;DR: The detection of murine leukemia virus antigens in complex cellular lysates was used to demonstrate the efficacy of this electrophoretic transfer technique.

8,346 citations

Journal ArticleDOI
01 Mar 1984-Cell
TL;DR: It is clear that detailed understanding of the mechanism of regulation of CAMP synthesis will soon be achieved from study of the interactions of purified components that have been reconstituted in lipid bilayers of defined composition.

1,645 citations

Journal ArticleDOI
01 Jul 1985-Cell
TL;DR: A polypeptide of Mr 38,000 has been identified as a specific component of the membrane of presynaptic vesicles, using the monoclonal antibody SY38, and this protein, for which the name synaptophysin*, is proposed, provides a molecular marker for the presyspheric membrane and may be involved in synaptic vesicle formation and exocytosis.

1,387 citations

Journal ArticleDOI
TL;DR: It is shown, by immunocytochemical techniques at the light microscopic and electron microscopic levels, that synapsin I is present in the majority of, and possibly in all, nerve terminals, where it is primarily associated with synaptic vesicles.
Abstract: Synapsin I (protein I) is a neuron-specific phosphoprotein, which is a substrate for cAMP-dependent and Ca/calmodulin-dependent protein kinases. In two accompanying studies (De Camilli, P., R. Cameron, and P. Greengard, and De Camilli, P., S. M. Harris, Jr., W. B. Huttner, and P. Greengard, 1983, J. Cell Biol. 96:1337-1354 and 1355-1373) we have shown, by immunocytochemical techniques at the light microscopic and electron microscopic levels, that synapsin I is present in the majority of, and possibly in all, nerve terminals, where it is primarily associated with synaptic vesicles. In the present study we have prepared a highly purified synaptic vesicle fraction from rat brain by a procedure that involves permeation chromatography on controlled-pore glass as a final purification step. Using immunological methods, synapsin I concentrations were determined in various subcellular fractions obtained in the course of vesicle purification. Synapsin I was found to copurify with synaptic vesicles and to represent approximately 6% of the total protein in the highly purified synaptic vesicle fraction. The copurification of synapsin I with synaptic vesicles was dependent on the use of low ionic strength media throughout the purification. Synapsin I was released into the soluble phase by increased ionic strength at neutral pH, but not by nonionic detergents. The highly purified synaptic vesicle fraction contained a calcium-dependent protein kinase that phosphorylated endogenous synapsin I in its collagenase-sensitive tail region. The phosphorylation of this region appeared to facilitate the dissociation of synapsin I from synaptic vesicles under the experimental conditions used.

1,156 citations


"Synuclein: a neuron-specific protei..." refers background in this paper

  • ...A number of molecules that are localized to the presynaptic nerve terminal have been identified, including synapsin I (Huttner et al., 1983; McCaffery and DeGennaro, 1986; Baines, 1987) tor 70 (Carlson and Kelly, 1983), synaptophysin (Matthew et al....

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