Protein complex found to control degradation of key proteins through a common pathway, according to JCI paper.
Researchers at Burnham Institute for Medical Research figured out what proteins generated by three Parkinson-associated genes form, how they function, and how mutant forms of the proteins impair this functioning.
PINK1, PARKIN, and DJ-1, which have all been linked to early-onset inherited forms of Parkinson’s disease. The Burnham Institute team found that the proteins created by these three genes form a complex in neuroblastoma cells and human brain lysates.
The Parkin/PINK1/DJ-1 complex was shown to control the degradation of certain proteins including Parkin itself in these cells and lysates. If the complex contained the mutant forms of either PINK1 or Parkin that are linked to Parkinson’s, its ability to degrade proteins was dramatically reduced, according to the scientists.
They therefore suggest that the proteins generated by PINK1, PARKIN, and DJ-1 function in a common pathway and that dysfunction in this pathway might underlie the development of Parkinson disease in individuals with mutations in these genes.
The team co-expressed vesicular stomatitis virus glycoprotein-tagged Parkin, flag-tagged PINK1, and mvc-tagged DJ-1 in various combinations in SH-SY5Y neuroblastoma cells and HEK293 cells.
The article appears in the February 23 issue of the Journal of Clinical Investigation.
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