Corpus ID: 34644033

Evidence That #-Synuclein Does Not Inhibit Phospholipase D †

@inproceedings{Rappley2009EvidenceT,
  title={Evidence That \#-Synuclein Does Not Inhibit Phospholipase D †},
  author={Irit Rappley and A. Gitler and Paige E. Selvy and M. Lavoie and B. Levy and H. Brown and S. Lindquist and D. Selkoe},
  year={2009}
}
R-Synuclein (RSyn) is a small cytosolic protein of unknown function, which is highly enriched in the brain. It is genetically linked to Parkinson’s disease (PD) in that missense mutations or multiplication of the gene encoding RSyn causes early onset familial PD. Furthermore, the neuropathological hallmarks of both sporadic and familial PD, Lewy bodies and Lewy neurites, contain insoluble aggregates of RSyn. Several studies have reported evidence that RSyn can inhibit phospholipase D (PLD… Expand

Figures from this paper

Alpha-Synuclein Function and Dysfunction on Cellular Membranes
TLDR
The known features of alpha-synuclein membrane interactions are reviewed in the context of both the putative functions of the protein and of its pathological roles in disease. Expand
Lipids at the Crossroad of α-Synuclein Function and Dysfunction: Biological and Pathological Implications
TLDR
An overview and discussion of the main findings relating to α-synuclein/lipid interaction and its involvement in the modulation of lipid metabolism and signaling are provided. Expand
Alpha-Synuclein in the Regulation of Brain Endothelial and Perivascular Cells: Gaps and Future Perspectives
TLDR
The main findings supporting how α-synuclein can affect ECs and/or BAMs function as well as their interplay and effect on other cells in the brain perivascular environment in physiological and pathological conditions are summarized. Expand
Intrinsically disordered proteins in synaptic vesicle trafficking and release
TLDR
The prevalence and functional roles of IDPs and IDRs associated with the release and recycling of synaptic vesicles at nerve terminals, as well as with the architecture of these terminals are reviewed to promote awareness of the importance of this class of proteins in these critical pathways and structures. Expand
Phospholipase D Signaling Pathways and Phosphatidic Acid as Therapeutic Targets in Cancer
TLDR
This review provides a comprehensive overview of the regulation of phospholipase D activity and its modulation of cellular signaling pathways and functions, particularly in cells that are under stress conditions. Expand

References

SHOWING 1-10 OF 44 REFERENCES
A combinatorial code for the interaction of alpha-synuclein with membranes.
TLDR
An in vitro binding assay to rafts purified from native membranes that binds with higher affinity to artificial membranes with the PS head group on the polyunsaturated fatty acyl chain rather than on the oleoyl side chain, indicating a stringent combinatorial code for the interaction of alpha-synuclein with membranes. Expand
Structural determinants of PLD2 inhibition by alpha-synuclein.
TLDR
It is concluded that PLD2 inhibition by alpha-synuclein is mediated by a lipid-stabilized alpha-helical structure in exon 4 and also by residues within exon 6, and that this inhibition can be modulated by phosphorylation of specific residues in exons 5 and 6. Expand
alpha-Synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase D activation in human embryonic kidney-293 cells.
TLDR
Co-transfection studies indicate that the association of alpha-synuclein with PLD, and modulation of PLD activity, is biologically important, but PLD does not appear to play an essential role in the pathophysiology ofalpha- Synuclein. Expand
α-Synuclein Blocks ER-Golgi Traffic and Rab1 Rescues Neuron Loss in Parkinson's Models
TLDR
Elevated expression of Rab1, the mammalian YPT1 homolog, protected against αSyn-induced dopaminergic neuron loss in animal models of PD, suggesting synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable. Expand
Relationships between the sequence of alpha-synuclein and its membrane affinity, fibrillization propensity, and yeast toxicity.
To investigate the alpha-synuclein protein and its role in Parkinson's disease, we screened a library of random point mutants both in vitro and in yeast to find variants in an unbiased way that couldExpand
Mice lacking alpha-synuclein display functional deficits in the nigrostriatal dopamine system.
TLDR
The hypothesis that alpha-Syn is an essential presynaptic, activity-dependent negative regulator of DA neurotransmission is supported. Expand
Synucleins Are Developmentally Expressed, and α-Synuclein Regulates the Size of the Presynaptic Vesicular Pool in Primary Hippocampal Neurons
TLDR
It is shown that the onset of α- and β-synuclein expression was delayed after synaptic development, suggesting that these synucleins may not be essential for synapse formation, and that one function ofα- synuclein may be to regulate the size of distinct pools of synaptic vesicles in mature neurons. Expand
The new mutation, E46K, of α‐synuclein causes parkinson and Lewy body dementia
TLDR
Dementia with Lewy bodies is related to mutation of α‐synuclein, and the novel mutation, that substitutes a dicarboxylic amino acid, glutamic acid, with a basic amino acid in a much conserved area of the protein, is likely to produce severe disturbance of protein function. Expand
α-Synuclein Overexpression in PC12 and Chromaffin Cells Impairs Catecholamine Release by Interfering with a Late Step in Exocytosis
TLDR
Overexpression of wild-type or A30P mutant α-syn in PC12 cell lines inhibited evoked catecholamine release without altering calcium threshold or cooperativity of release, and inhibits a vesicle “priming” step, after secretory vesicular trafficking to “docked” sites but before calcium-dependent vesicles membrane fusion. Expand
alpha-Synuclein membrane interactions and lipid specificity.
TLDR
The results suggest that alpha-Syn membrane interactions are physiologically important and the lipid composition of the cellular membranes may affect these interactions in vivo. Expand
...
1
2
3
4
5
...