VPS35, the Retromer Complex and Parkinson’s Disease

VPS35, the Retromer Complex and Parkinson’s Disease

Mutations in the vacuolar protein sorting 35 ortholog (VPS35) gene encoding a core component of the retromer complex, have recently emerged as a new cause of late-onset, autosomal dominant familial Parkinson's disease (PD). A single missense mutation, AspD620Asn (D620N), has so far been unambiguously identified to cause PD in multiple individuals and families worldwide. The exact molecular mech...

Retromer Binding to FAM21 and the WASH Complex Is Perturbed by the Parkinson Disease-Linked VPS35(D620N) Mutation

Retromer is a protein assembly that plays a central role in orchestrating export of transmembrane-spanning cargo proteins from endosomes into retrieval pathways destined for the Golgi apparatus and the plasma membrane [1]. Recently, a specific mutation in the retromer component VPS35, VPS35(D620N), has linked retromer dysfunction to familial autosomal dominant and sporadic Parkinson disease [2,...

Vps35 R524W mutation impairs the fuction of retromer

Retromer-dependent neurotransmitter receptor trafficking to synapses is altered by the Parkinson's disease VPS35 mutation p.D620N.

Vacuolar protein sorting 35 (VPS35) is a core component of the retromer complex, crucial to endosomal protein sorting and intracellular trafficking. We recently linked a mutation in VPS35 (p.D620N) to familial parkinsonism. Here, we characterize human VPS35 and retromer function in mature murine neuronal cultures and investigate neuron-specific consequences of the p.D620N mutation. We find VPS3...

The VPS35 gene and Parkinson's disease.

Parkinson's disease (PD), the second most common age-related neurodegenerative disease, is characterized by loss of dopaminergic and nondopaminergic neurons, leading to a variety of motor and nonmotor symptoms. In addition to environmental factors, genetic predisposition and specific gene mutations have been shown to play an important role in the pathogenesis of this disorder. Recently, the ide...