GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:16227987

From GONUTS
Jump to: navigation, search
Citation

LaVoie, MJ, Ostaszewski, BL, Weihofen, A, Schlossmacher, MG and Selkoe, DJ (2005) Dopamine covalently modifies and functionally inactivates parkin. Nat. Med. 11:1214-21

Abstract

Inherited mutations in PARK2, the gene encoding parkin, cause selective degeneration of catecholaminergic neurons in the substantia nigra and locus coeruleus of the brainstem, resulting in early-onset parkinsonism. But the role of parkin in common, sporadic forms of Parkinson disease remains unclear. Here we report that the neurotransmitter dopamine covalently modifies parkin in living dopaminergic cells, a process that increases parkin insolubility and inactivates its E3 ubiquitin ligase function. In the brains of individuals with sporadic Parkinson disease, we observed decreases in parkin solubility consistent with its functional inactivation. Using a new biochemical method, we detected catechol-modified parkin in the substantia nigra but not other regions of normal human brain. These findings show a vulnerability of parkin to modification by dopamine, the principal transmitter lost in Parkinson disease, suggesting a mechanism for the progressive loss of parkin function in dopaminergic neurons during aging and sporadic Parkinson disease.

Links

PubMed Online version:10.1038/nm1314

Keywords

Adult; Animals; Blotting, Western; Brain Chemistry; CHO Cells; Carbon Radioisotopes/metabolism; Cell Line; Cells, Cultured; Cricetinae; Dopamine/metabolism; Dopamine/toxicity; Dopamine Agents/pharmacology; Dose-Response Relationship, Drug; Female; Humans; Locus Coeruleus/cytology; Locus Coeruleus/metabolism; Methamphetamine/pharmacology; Mutation; Neurons/drug effects; Parkinson Disease/genetics; Parkinson Disease/metabolism; Precipitin Tests; Solubility; Substantia Nigra/cytology; Substantia Nigra/metabolism; Ubiquitin-Protein Ligases/chemistry; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:PRKN

involved_in

GO:0000209: protein polyubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PRKN

enables

GO:0061630: ubiquitin protein ligase activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(UniProtKB:O15354)

Seeded From UniProt

complete

HUMAN:PRKN2

enables

GO:0061630: ubiquitin protein ligase activity

ECO:0000314: direct assay evidence used in manual assertion

F

has_direct_input:(UniProtKB:O15354)

Seeded From UniProt

complete

HUMAN:PRKN2

involved_in

GO:0000209: protein polyubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.