Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson’s disease

Zhong-Can Chen; Wei Zhang; Ling-Ling Chua; Chou Chai; Rong Li; Lin Lin; Zhen Cao; Dario C. Angeles; Lawrence W. Stanton; Jian-He Peng; Zhi-Dong Zhou; Kah-Leong Lim; Li Zeng; Eng-King Tan

doi:10.1126/scisignal.aam6790

Research ArticleNeurodegeneration

Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson’s disease

View ORCID ProfileZhong-Can Chen¹,
View ORCID ProfileWei Zhang¹,
Ling-Ling Chua²,
View ORCID ProfileChou Chai³,
Rong Li⁴,
Lin Lin⁵,⁶,
Zhen Cao¹,
Dario C. Angeles²,*,
Lawrence W. Stanton⁵,
Jian-He Peng⁴,†,
View ORCID ProfileZhi-Dong Zhou²,⁷,
View ORCID ProfileKah-Leong Lim³,⁷,⁸,
View ORCID ProfileLi Zeng¹,⁷,‡, and
View ORCID ProfileEng-King Tan²,⁷,⁹,‡

¹Neural Stem Cell Research Laboratory, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.
²Research Department, National Neuroscience Institute, Singapore General Hospital (SGH) Campus, Singapore 169856, Singapore.
³Neurodegeneration Laboratory, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.
⁴Analytical Mass Spectrometry Laboratory, Experimental Therapeutics Centre, Agency of Science, Technology and Research (A*STAR), Singapore 138669, Singapore.
⁵Stem Cell and Developmental Biology Group, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore.
⁶National University of Singapore (NUS) Graduate School for Integrative Sciences and Engineering, NUS, Singapore 117456, Singapore.
⁷Neuroscience and Behavioral Disorders Program, DUKE-NUS Graduate Medical School, Singapore 169857, Singapore.
⁸Department of Physiology, Yong Loo Lin School of Medicine, NUS, Singapore 117597, Singapore.
⁹Department of Neurology, National Neuroscience Institute, SGH Campus, Singapore 169856, Singapore.

↵‡Corresponding author. Email: li_zeng{at}nni.com.sg (L.Z.); tan.eng.king{at}sgh.com.sg (E.-K.T.)

↵* Present address: Department of Paediatrics and Psychology, #15-01 MD1, 12 Science Drive 2, Yong Loo Lin School of Medicine, NUS, Singapore 117549, Singapore.
↵† Present address: National Collection of Type Cultures, Public Health England, London NW95HT, UK.

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Science Signaling 18 Jul 2017:
Vol. 10, Issue 488, eaam6790
DOI: 10.1126/scisignal.aam6790

Zhong-Can Chen

1Neural Stem Cell Research Laboratory, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.

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Wei Zhang

1Neural Stem Cell Research Laboratory, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.

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Ling-Ling Chua

2Research Department, National Neuroscience Institute, Singapore General Hospital (SGH) Campus, Singapore 169856, Singapore.

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Chou Chai

3Neurodegeneration Laboratory, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.

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Rong Li

4Analytical Mass Spectrometry Laboratory, Experimental Therapeutics Centre, Agency of Science, Technology and Research (A*STAR), Singapore 138669, Singapore.

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Lin Lin

5Stem Cell and Developmental Biology Group, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore.

6National University of Singapore (NUS) Graduate School for Integrative Sciences and Engineering, NUS, Singapore 117456, Singapore.

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Zhen Cao

1Neural Stem Cell Research Laboratory, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.

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Dario C. Angeles

2Research Department, National Neuroscience Institute, Singapore General Hospital (SGH) Campus, Singapore 169856, Singapore.

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Lawrence W. Stanton

5Stem Cell and Developmental Biology Group, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore.

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Jian-He Peng

4Analytical Mass Spectrometry Laboratory, Experimental Therapeutics Centre, Agency of Science, Technology and Research (A*STAR), Singapore 138669, Singapore.

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Zhi-Dong Zhou

2Research Department, National Neuroscience Institute, Singapore General Hospital (SGH) Campus, Singapore 169856, Singapore.

7Neuroscience and Behavioral Disorders Program, DUKE-NUS Graduate Medical School, Singapore 169857, Singapore.

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Kah-Leong Lim

3Neurodegeneration Laboratory, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.

7Neuroscience and Behavioral Disorders Program, DUKE-NUS Graduate Medical School, Singapore 169857, Singapore.

8Department of Physiology, Yong Loo Lin School of Medicine, NUS, Singapore 117597, Singapore.

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Li Zeng

1Neural Stem Cell Research Laboratory, Research Department, National Neuroscience Institute, Singapore 308433, Singapore.

7Neuroscience and Behavioral Disorders Program, DUKE-NUS Graduate Medical School, Singapore 169857, Singapore.

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For correspondence: Li_Zeng@nni.com.sg tan.eng.king@sgh.com.sg

Eng-King Tan

2Research Department, National Neuroscience Institute, Singapore General Hospital (SGH) Campus, Singapore 169856, Singapore.

7Neuroscience and Behavioral Disorders Program, DUKE-NUS Graduate Medical School, Singapore 169857, Singapore.

9Department of Neurology, National Neuroscience Institute, SGH Campus, Singapore 169856, Singapore.

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For correspondence: Li_Zeng@nni.com.sg tan.eng.king@sgh.com.sg

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Phosphorylation of amyloid precursor protein by mutant LRRK2 promotes AICD activity and neurotoxicity in Parkinson’s disease

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