VPS35

VPS35

Vacuolar protein sorting ortholog 35 (VPS35) is a protein coding gene and a protein complex involved in autophagy and functions by recycling protein cargoes. The protein makes up a core subunit of a heteropentameric complex, known as the retromer. The retromer consists of two main components, the cargo-selective complex trimer (CSC) and the sorting nexin dimer (SNX). Components of the retromer and their associated proteins are involved in the transportation of cargo proteins from the endosomal system to the trans-Golgi network or the plasma membrane. The CSC, made up of VPS26, VPS29, and VPS35, locates to the endosomal membrane and recognizes transmembrane proteins to be sorted. VPS35 makes up the largest component of the CSC proteins and its function is essential for proper transport and recycling of cargo proteins[1].

 

cdc

Interactive model from Swiss-Model

The endolysosomal system is implicated in the function and cell control of homeostasis, and disruptions within the system play a role in both Alzheimer's and Parkinson's disease[2]. Evidence suggests that missense mutations in the VPS35 coding gene lead to retromer dysfunction and may contribute to late-onset autosomal dominant Parkinson's disease via the single AspD620Asn (D620N) missense mutation. Adeno-associated virus (AAV)-mediated overexpression of D620N VPS35 in the substantia nigra resulted in degeneration of dopaminergic neurons, making the D620N mutation worthy of deeper study. 

 

1. Williams ET, Chen X, Moore DJ. VPS35, the Retromer Complex and Parkinson's Disease. J Parkinsons Dis. 2017;7(2):219-233. doi: 10.3233/JPD-161020.  

2. Williams ET, Chen X, Otero PA, Moore DJ. Understanding the contributions of VPS35 and the retromer in neurodegenerative disease. Neurobiol Dis. 2022 Aug;170:105768. doi: 10.1016/j.nbd.2022.105768.