α-Synuclein Disrupts Stress Signaling by Inhibiting Polo-like Kinase Cdc5/Plk2

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2012 Sep 19

PMID 22988096

Citations 28

Authors

Shaoxiao Wang

Baoshan Xu

Liang-Chun Liou

Qun Ren

Shile Huang

Yan Luo

Zhaojie Zhang

Stephan N Witt

Affiliations

Soon will be listed here.

Abstract

Parkinson disease (PD) results from the slow, progressive loss of dopaminergic neurons in the substantia nigra. Alterations in α-synuclein (aSyn), such as mutations or multiplications of the gene, are thought to trigger this degeneration. Here, we show that aSyn disrupts mitogen-activated protein kinase (MAPK)-controlled stress signaling in yeast and human cells, which results in inefficient cell protective responses and cell death. aSyn is a substrate of the yeast (and human) polo-like kinase Cdc5 (Plk2), and elevated levels of aSyn prevent Cdc5 from maintaining a normal level of GTP-bound Rho1, which is an essential GTPase that regulates stress signaling. The nine N-terminal amino acids of aSyn are essential for the interaction with polo-like kinases. The results support a unique mechanism of PD pathology.

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