α-Synuclein interacts with Phospholipase D Isozymes and Inhibits Pervanadate-induced Phospholipase D Activation in Human Embryonic Kidney-293 Cells

Authors
Bong-Hyun AhnHyangshuk RhimShi Yeon KimYoung-Mo SungMun-Yong LeeJu-Youn ChoiBenjamin WolozinJong-Soo ChangYoung Han LeeTaeg Kyu KwonKwang Chul ChungShin-Hee YoonSang June HahnMyung-Suk KimYang-Hyeok JoDo Sik Min
Department
Dept. of Immunology (면역학)
Issue Date
2002
Citation
Journal of Biological Chemistry, Vol.277(14) : 12334-12342, 2002
ISSN
0021-9258
Abstract
α-Synuclein has been implicated in the pathogenesis of many neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Although the function of α-synuclein remains largely unknown, recent studies have demonstrated that this protein can interact with phospholipids. To address the role of α-synuclein in neurodegenerative disease, we have investigated whether it binds phospholipase D (PLD) and affects PLD activity in human embryonic kidney (HEK)-293 cells overexpressing wild type α-synuclein or the mutant forms of α-synuclein (A53T, A30P) associated with Parkinson's disease. Tyrosine phosphorylation of α-synuclein appears to play a modulatory role in the inhibition of PLD, because mutation of Tyr125 to Phe slightly increases inhibitory effect of α-synuclein on PLD activity. Treatment with pervanadate or phorbol myristate acetate inhibits PLD more in HEK 293 cells overexpressing α-synuclein than in control cells. Binding of α-synuclein to PLD requires phox and pleckstrin homology domain of PLD and the amphipathic repeat region and non-Aβ component of α-synuclein. Although biologically important, co-transfection studies indicate that the interaction of α-synuclein with PLD does not influence the tendency of α-synuclein to form pathological inclusions. These results suggest that the association of α-synuclein with PLD, and modulation of PLD activity, is biologically important, but PLD does not appear to play an essential role in the pathophysiology of α-synuclein.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/33740
Appears in Collections:
1. Journal Papers (연구논문) > 1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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