Role of α-synuclein in synaptic glutamate release

Gureviciene, Irina; Gurevicius, Kestutis; Tanila, Heikki

doi:10.1016/j.nbd.2007.06.016

Cited by 86 publications

(80 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…What is happening upon a-synuclein knockout? Here studies report decreased exocytosis [33,35,37,38], no change [36,39], or even increased exocytosis [40][41][42] (Table 2). However, these studies need to be interpreted with care because a-synuclein is not the only synuclein isoform, and loss of physiological function could possibly be compensated by b-or g-synuclein.…”

Section: Function Of A-synuclein On Synaptic Activity and Transmittermentioning

confidence: 64%

“…Recent work in Parkinson's disease models with overexpression of wild-type a-synuclein show mainly an inhibitory effect of a-synuclein on neurotransmitter release [29][30][31][32][33][34], whereas two other studies come to the opposite conclusions [35,36]. In one of the latter increased synaptic activity was found in cultured hippocampal neurons acutely injected with a-synuclein.…”

Section: Function Of A-synuclein On Synaptic Activity and Transmittermentioning

confidence: 95%

See 1 more Smart Citation

α-Synuclein – Regulator of Exocytosis, Endocytosis, or Both?

Lautenschläger

Kaminski

Schierle

2017

Trends in Cell Biology

121

124

View full text Add to dashboard Cite

a-Synuclein is known as a presynaptic protein that binds to small synaptic vesicles. Recent studies suggest that a-synuclein is not only attracted to these tiny and therewith highly curved membranes, but that in fact the sensing and regulation of membrane curvature is part of its physiological function. Moreover, recent studies have suggested that a-synuclein plays a role in the endocytosis of synaptic vesicles, and have provided support for a function of a-synuclein during exo-and endocytosis in which curvature sensing and membrane stabilization are crucial steps. This review aims to highlight recent research in the field and adds a new picture on the function of a-synuclein in maintaining synaptic homeostasis upon intense and repetitive neuronal activity.

show abstract

Section: Function Of A-synuclein On Synaptic Activity and Transmittermentioning

confidence: 64%

Section: Function Of A-synuclein On Synaptic Activity and Transmittermentioning

confidence: 95%

α-Synuclein – Regulator of Exocytosis, Endocytosis, or Both?

Lautenschläger

Kaminski

Schierle

2017

Trends in Cell Biology

121

124

View full text Add to dashboard Cite

show abstract

“…A physiological role for vesicle binding by ␣-synuclein is suggested by the observation that in PC12 and chromaffin cells ␣-synuclein appears to be a negative regulator of synaptic vesicle exocytosis and neurotransmitter release (4). In addition, loss of ␣-synuclein in cell culture or in mice results in a significant decrease in the population of presynaptic vesicles in the resting or reserve pool (5)(6)(7). Further support for a role of ␣-synuclein in vesicular trafficking comes from modifier screens in Caenorhabditis elegans showing that the toxicity that arises from expression of ␣-synuclein may be modified by proteins involved in vesicle trafficking (8,9).…”

mentioning

confidence: 99%

Proteomics Analysis Identifies Phosphorylation-dependent α-Synuclein Protein Interactions

McFarland

Ellis

Markey

et al. 2008

Molecular & Cellular Proteomics

162

143

View full text Add to dashboard Cite

Mutations and copy number variation in theHere we used the combination of peptide pulldown assays and mass spectrometry to identify and compare protein-protein interactions of phosphorylated and nonphosphorylated ␣-synuclein. We showed that non-phosphorylated ␣-synuclein carboxyl terminus pulled down protein complexes that were highly enriched for mitochondrial electron transport proteins, whereas ␣-synuclein carboxyl terminus phosphorylated on either Ser-129 or Tyr-125 did not. Instead the set of proteins pulled down by phosphorylated ␣-synuclein was highly enriched in certain cytoskeletal proteins, in vesicular trafficking proteins, and in a small number of enzymes involved in protein serine phosphorylation. This targeted comparative proteomics approach for unbiased identification of protein-protein interactions sug-

show abstract

“…In mature cultured primary neurons, synucleins co-localize almost exclusively with synaptophysin in the presynaptic terminals and appear earlier than synaptophysin, but later than the vesicleassociated protein synapsin I during CNS development (Hsu et al 1998;Jensen et al 1999;Murphy et al 2000;Withers et al 1997). Additional recent studies have shown that α-synuclein may be required for the genesis and/or maintenance of resting pools of presynaptic vesicles (Cabin et al 2002;Gureviciene et al 2007;Murphy et al 2000). Recent work has also shown that α-synuclein can potentiate Ca 2+ influx through voltagedependent Ca 2+ channels (Adamczyk and Strosznajder 2006;Ueda et al 1997).…”

Section: Discussionmentioning

confidence: 99%

“…This had led to the hypothesis that synucleins may be involved in synaptic membrane biogenesis and vesicle budding (Tofaris and Spillantini 2007). Other recent studies have implicated α-synuclein in glutamate release (Gureviciene et al 2007). Additional work has demonstrated that α-synuclein may be required for the genesis or maintenance of presynaptic neurotransmitter vesicle numbers and mobilization (Cabin et al 2002;Murphy et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Localization of Synucleins in the Mammalian Cochlea

Akil

Weber

Park

et al. 2008

JARO

View full text Add to dashboard Cite

Synucleins are widely expressed synaptic proteins within the central nervous system that have been implicated in such neurodegenerative disorders as Parkinson's disease. In this study, an initial characterization of all three synucleins, α-, β-, and γ-synuclein, within the cochlea was undertaken. Reverse transcriptase-polymerase chain reaction (PCR) demonstrated all three synuclein mRNA species within microdissected cochlear tissue. Quantitative PCR suggests that β-synuclein is the most abundantly expressed form, followed by γ-and then α-synuclein. Western blot analysis similarly demonstrates all three synuclein proteins within microdissected cochlear tissue. Immunofluorescence localizes the three synucleins predominantly to the efferent neuronal system at the efferent outer hair cell synapse, with some additional localization within the efferent tunnel-crossing fibers (α-and γ-synuclein), spiral ganglion (β-synuclein), inner spiral bundle (γ-synuclein), and stria vascularis (α-9 β-synuclein). Developmentally, γ-synuclein can be seen in the region of the outer hair cells by E19, while α-and β-synuclein do not clearly appear there until~P10. Additional studies in a null-mutant γ-synuclein mouse show no histological changes in the organ of Corti with normal hair cell and spiral ganglion cell counts, and normal ABR and DPOAE thresholds in wild-type vs mutant littermates. Together, these results localize synucleins to the efferent cholinergic neuronal auditory system, pointing to a role in normal auditory function, and raising the potential implications for their role in auditory neurodegenerative disorders. However, γ-synuclein alone is not required for the development and maintenance of normal hearing through P21. Whether overlapping roles of the other synucleins help compensate for the loss of γ-synuclein remains to be determined.

show abstract

Role of α-synuclein in synaptic glutamate release

Cited by 86 publications

References 23 publications

α-Synuclein – Regulator of Exocytosis, Endocytosis, or Both?

α-Synuclein – Regulator of Exocytosis, Endocytosis, or Both?

Proteomics Analysis Identifies Phosphorylation-dependent α-Synuclein Protein Interactions

Localization of Synucleins in the Mammalian Cochlea

Contact Info

Product

Resources

About