Language:

Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions

The Journal of neuroscience, 2010-03, Vol.30 (9), p.3184-3198 [Peer Reviewed Journal]

Copyright © 2010 the authors 0270-6474/10/303184-15$15.00/0 2010 ;ISSN: 0270-6474 ;EISSN: 1529-2401 ;DOI: 10.1523/JNEUROSCI.5922-09.2010 ;PMID: 20203178

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions
Author: Paleologou, Katerina E ; Oueslati, Abid ; Shakked, Gideon ; Rospigliosi, Carla C ; Kim, Hai-Young ; Lamberto, Gonzalo R ; Fernandez, Claudio O ; Schmid, Adrian ; Chegini, Fariba ; Gai, Wei Ping ; Chiappe, Diego ; Moniatte, Marc ; Schneider, Bernard L ; Aebischer, Patrick ; Eliezer, David ; Zweckstetter, Markus ; Masliah, Eliezer ; Lashuel, Hilal A
Subjects: alpha-Synuclein - chemistry ; alpha-Synuclein - metabolism ; Alzheimer Disease - genetics ; Alzheimer Disease - metabolism ; Alzheimer Disease - physiopathology ; Amino Acid Sequence - physiology ; Animals ; Brain - metabolism ; Brain - pathology ; Cell Membrane - metabolism ; Creatine Kinase - genetics ; Creatine Kinase - metabolism ; Disease Models, Animal ; Humans ; Lewy Bodies - genetics ; Lewy Bodies - metabolism ; Lewy Bodies - pathology ; Lewy Body Disease - genetics ; Lewy Body Disease - metabolism ; Lewy Body Disease - physiopathology ; Male ; Mice ; Mice, Transgenic ; Multiple System Atrophy - genetics ; Multiple System Atrophy - metabolism ; Multiple System Atrophy - physiopathology ; Neurodegenerative Diseases - genetics ; Neurodegenerative Diseases - metabolism ; Neurodegenerative Diseases - physiopathology ; Neurons - metabolism ; Parkinson Disease - genetics ; Parkinson Disease - metabolism ; Parkinson Disease - physiopathology ; Phosphorylation ; Polymers - metabolism ; Protein Isoforms - genetics ; Protein Isoforms - metabolism ; Rats ; Rats, Wistar ; Serine - metabolism
Is Part Of: The Journal of neuroscience, 2010-03, Vol.30 (9), p.3184-3198
Description: Increasing evidence suggests that phosphorylation may play an important role in the oligomerization, fibrillogenesis, Lewy body (LB) formation, and neurotoxicity of alpha-synuclein (alpha-syn) in Parkinson disease. Herein we demonstrate that alpha-syn is phosphorylated at S87 in vivo and within LBs. The levels of S87-P are increased in brains of transgenic (TG) models of synucleinopathies and human brains from Alzheimer disease (AD), LB disease (LBD), and multiple system atrophy (MSA) patients. Using antibodies against phosphorylated alpha-syn (S129-P and S87-P), a significant amount of immunoreactivity was detected in the membrane in the LBD, MSA, and AD cases but not in normal controls. In brain homogenates from diseased human brains and TG animals, the majority of S87-P alpha-syn was detected in the membrane fractions. A battery of biophysical methods were used to dissect the effect of S87 phosphorylation on the structure, aggregation, and membrane-binding properties of monomeric alpha-syn. These studies demonstrated that phosphorylation at S87 expands the structure of alpha-syn, increases its conformational flexibility, and blocks its fibrillization in vitro. Furthermore, phosphorylation at S87, but not S129, results in significant reduction of alpha-syn binding to membranes. Together, our findings provide novel mechanistic insight into the role of phosphorylation at S87 and S129 in the pathogenesis of synucleinopathies and potential roles of phosphorylation in alpha-syn normal biology.
Publisher: United States: Society for Neuroscience
Language: English
Identifier: ISSN: 0270-6474
EISSN: 1529-2401
DOI: 10.1523/JNEUROSCI.5922-09.2010
PMID: 20203178
Source: Geneva Foundation Free Medical Journals
MEDLINE
PubMed Central
Alma/SFX Local Collection

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions

Copyright © 2010 the authors 0270-6474/10/303184-15$15.00/0 2010 ;ISSN: 0270-6474 ;EISSN: 1529-2401 ;DOI: 10.1523/JNEUROSCI.5922-09.2010 ;PMID: 20203178

Searching Remote Databases, Please Wait