This report describes a Parkinson-like neurodegenerative disease model using the Drosophila Rpt2 gene, the Drosophila gene orthologous to the human proteasome subunit PSMC1. Rpt2 and PSMC1 encode one of the proteasome regulatory subunit ATPases (see FBgg0001557). RNAi-targeting constructs, a targeted CRISPR knockout construct, and other genetic reagents have been generated for Rpt2.
The human PSMC1 gene has not been introduced into flies.
Dysfunction of the proteasome-ubiquitin system is causative or is observed as a downstream event in a number of neurodegenerative diseases (see FBhh0000862 for examples modeled in Drosophila). In order to characterize the role of the different proteasome subunits in dopaminergic neuron degeneration, RNAi targeting various different proteasome subunit genes in Drosophila was used to assess neurodegeneration phenotypes. The Rpt2 gene was chosen for more detailed characterization, using RNAi-effected knockdown and different neuronal drivers. Pan-neuronal knockdown results in locomotor defects and lethality in the larval stage. Reduction of Rpt2 in adult dopaminergic neurons causes reduced survival, hyperactivity, neurodegeneration, and sleep loss.
[updated Oct. 2020 by FlyBase; FBrf0222196]
See report for Parkinson disease (FBhh0000004).
PSMC1 encodes a component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins. [Gene Cards, PSMC1; 2020.10.27]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human PSMC1 (1 Drosophila to 1 human). Dmel\Rpt2 shares 91% identity and 96% similarity with the human gene.
