Parkinson's disease-associated α-synuclein is a calmodulin substrate Journal Article
| Authors: | Martinez, J.; Moeller, I.; Erdjument-Bromage, H.; Tempst, P.; Lauring, B. |
| Article Title: | Parkinson's disease-associated α-synuclein is a calmodulin substrate |
| Abstract: | α-Synuclein is a neuronal protein thought to be central in the pathogenesis of Parkinson's disease (PD) because it comprises the fibrillar core of Lewy bodies, one of the histologically defining lesions of PD, and because mutations in α-synuclein cause autosomal dominant PD. Although its physiologic role is uncertain, α-synuclein is a synaptic protein that may contribute to plasticity. We produced synuclein with incorporated photoprobes to identify and purify novel synuclein-interacting proteins both to begin to clarify the physiology of synuclein and to identify factors that may regulate synuclein conformation. We detected several cross-links and purified and identified one as calmodulin (CaM). CaM binds to both wild type and PD-associated mutant α-synucleins in a calcium-dependent manner. We further demonstrate that CaM and α-synuclein interact in intact cells in a calcium-dependent manner and that activated CaM accelerates the formation of synuclein fibrils in vitro. We hypothesize that the known calcium control of synuclein function is mediated through CaM interaction and that CaM potentially alters synuclein conformation. |
| Keywords: | nonhuman; protein conformation; proteins; protein analysis; mouse; metabolism; animal tissue; nerve tissue proteins; protein binding; genetic transcription; physiology; animalia; chemistry; brain; messenger rna; substrate specificity; recombinant protein; nerve cell plasticity; rna translation; transfer rna; disease control; parkinson disease; enzyme specificity; neurologic disease; nerve protein; mutagenesis; degenerative disease; cytosol; conformations; biochemical engineering; plasticity; cross linking; lewy body; alpha-synuclein; calmodulin; synucleins; humans; human; priority journal; article; alpha synuclein; photoprobes; snca protein, human; synuclein |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 278 |
| Issue: | 19 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 2003-05-09 |
| Start Page: | 17379 |
| End Page: | 17387 |
| Language: | English |
| DOI: | 10.1074/jbc.M209020200 |
| PUBMED: | 12610000 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
