Dec 7, 2017

The functional roles of retromer in Parkinson's disease

FEBS Letters
Yi CuiRohan D Teasdale

Abstract

The endosomal system is critical for the maintenance of intracellular homeostasis, and defects in this system are often linked to neurological disorders. The retromer complex is a critical coordinator of endosomal dynamics and has functional roles in multiple cellular processes through sorting cargoes from endosomes to the trans-Golgi network (TGN) or to the plasma membrane. Mammalian retromer comprises a core Vps26-Vps35-Vps29 trimer and associates with a range of proteins to generate endosomal tubular-vesicular carriers. Alterations in retromer function or its molecular organization have been a rising risk factor for Parkinson's disease (PD). Although genetic evidence has shown several variants within retromer in late-onset PD cases, the exact molecular machineries by which retromer variants induce the development of PD are still not completely elucidated. In this Review, we will focus on the functional roles of retromer in neuronal health, summarize advances in defining the cellular pathological phenotype caused by retromer deficiency or PD-linked retromer variants and discuss the potential clues of how retromer deregulation may contribute to PD pathogenesis.

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Mentioned in this Paper

Pathogenic Aspects
Trans-Golgi Region
Cellular Process
Pathogenesis
Complex (molecular entity)
Protoplasm
Neurons
Protein Deregulation
VPS29 protein, human
Molecular_function

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