α-synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase d activation in human embryonic kidney-293 cells

Bong Hyun Ahn, Hyangshuk Rhim, Young Mo Sung Shi Yeon Kim, Mun Yong Lee, Ju Youn Choi, Benjamin Wolozin, Jong Soo Chang, Young Han Lee, Taeg Kyu Kwon, Kwang Chul Chung, Shin Hee Yoon, Sang June Hahn, Myung Suk Kim, Yang Hyeok Jo, Do Sik Mina

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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.

Original languageEnglish
Pages (from-to)12334-12342
Number of pages9
JournalJournal of Biological Chemistry
Volume277
Issue number14
DOIs
Publication statusPublished - 2002 Apr 5

Fingerprint

Synucleins
Phospholipase D
Phospholipases
Isoenzymes
Chemical activation
Kidney
Neurodegenerative diseases
pervanadate
Neurodegenerative Diseases
Parkinson Disease
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ahn, Bong Hyun ; Rhim, Hyangshuk ; Shi Yeon Kim, Young Mo Sung ; Lee, Mun Yong ; Choi, Ju Youn ; Wolozin, Benjamin ; Chang, Jong Soo ; Lee, Young Han ; Kwon, Taeg Kyu ; Chung, Kwang Chul ; Yoon, Shin Hee ; Hahn, Sang June ; Kim, Myung Suk ; Jo, Yang Hyeok ; Mina, Do Sik. / α-synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase d activation in human embryonic kidney-293 cells. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 14. pp. 12334-12342.
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title = "α-synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase d activation in human embryonic kidney-293 cells",
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.",
author = "Ahn, {Bong Hyun} and Hyangshuk Rhim and {Shi Yeon Kim}, {Young Mo Sung} and Lee, {Mun Yong} and Choi, {Ju Youn} and Benjamin Wolozin and Chang, {Jong Soo} and Lee, {Young Han} and Kwon, {Taeg Kyu} and Chung, {Kwang Chul} and Yoon, {Shin Hee} and Hahn, {Sang June} and Kim, {Myung Suk} and Jo, {Yang Hyeok} and Mina, {Do Sik}",
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Ahn, BH, Rhim, H, Shi Yeon Kim, YMS, Lee, MY, Choi, JY, Wolozin, B, Chang, JS, Lee, YH, Kwon, TK, Chung, KC, Yoon, SH, Hahn, SJ, Kim, MS, Jo, YH & Mina, DS 2002, 'α-synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase d activation in human embryonic kidney-293 cells', Journal of Biological Chemistry, vol. 277, no. 14, pp. 12334-12342. https://doi.org/10.1074/jbc.M110414200

α-synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase d activation in human embryonic kidney-293 cells. / Ahn, Bong Hyun; Rhim, Hyangshuk; Shi Yeon Kim, Young Mo Sung; Lee, Mun Yong; Choi, Ju Youn; Wolozin, Benjamin; Chang, Jong Soo; Lee, Young Han; Kwon, Taeg Kyu; Chung, Kwang Chul; Yoon, Shin Hee; Hahn, Sang June; Kim, Myung Suk; Jo, Yang Hyeok; Mina, Do Sik.

In: Journal of Biological Chemistry, Vol. 277, No. 14, 05.04.2002, p. 12334-12342.

Research output: Contribution to journalArticle

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T1 - α-synuclein interacts with phospholipase D isozymes and inhibits pervanadate-induced phospholipase d activation in human embryonic kidney-293 cells

AU - Ahn, Bong Hyun

AU - Rhim, Hyangshuk

AU - Shi Yeon Kim, Young Mo Sung

AU - Lee, Mun Yong

AU - Choi, Ju Youn

AU - Wolozin, Benjamin

AU - Chang, Jong Soo

AU - Lee, Young Han

AU - Kwon, Taeg Kyu

AU - Chung, Kwang Chul

AU - Yoon, Shin Hee

AU - Hahn, Sang June

AU - Kim, Myung Suk

AU - Jo, Yang Hyeok

AU - Mina, Do Sik

PY - 2002/4/5

Y1 - 2002/4/5

N2 - 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.

AB - 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.

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