Endosomal recycling protein Rab11 in Parkin and Pink1 signaling in Drosophila model of Parkinson's disease

Exp Cell Res. 2022 Nov 15;420(2):113357. doi: 10.1016/j.yexcr.2022.113357. Epub 2022 Sep 15.

Abstract

Neurodegenerative diseases are progressive disorders of the nervous system primarily affecting the loss of neuronal cells present in the brain. Although most neurodegenerative cases are sporadic, some familial genes are found to be involved in the neurodegenerative diseases. The extensively studied parkin and pink1 gene products are known to be involved in the removal of damaged mitochondria via autophagy (mitophagy), a quality control process. If the function of any of these genes is somehow disrupted, accumulation of damaged mitochondria occurs in the forms of protein aggregates in the cytoplasm, leading to formation of the Lewy-bodies. Autophagy is an important catabolic process where the endosomal Rab proteins are seen to be involved. Rab11, an endosomal recycling protein, serves as an ATG9A carrier that helps in autophagosome formation and maturation. Earlier studies have reported that loss of Rab11 prevents the fusion of autophagosomes with the late endosomes hampering the autophagy pathway resulting in apoptosis of cells. In this study, we have emphasized on the importance and functional role of Rab11 in the molecular pathway of Parkin/Pink1 in Parkinson's disease.

Keywords: ATG9A; Autophagosomes; Dopaminergic neuron; Drosophila; Mitophagy; Neurodegenerative diseases; Parkin/Pink1; Parkinson's disease; Rab proteins; Rab11; Recycling endosome; Vesicle trafficking; α-Synuclein.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila / metabolism
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Endosomes / metabolism
  • PTEN-Induced Putative Kinase
  • Parkinson Disease* / genetics
  • Parkinson Disease* / metabolism
  • Protein Aggregates
  • Protein Serine-Threonine Kinases
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism
  • rab11 GTP-Binding Proteins

Substances

  • Drosophila Proteins
  • Protein Aggregates
  • Protein Serine-Threonine Kinases
  • Ubiquitin-Protein Ligases
  • rab GTP-Binding Proteins
  • PINK1 protein, Drosophila
  • PTEN-Induced Putative Kinase
  • Rab11 protein, Drosophila
  • rab11 GTP-Binding Proteins