In recent years, genomic, animal and cell biology studies have implicated deficiencies in
retromer-mediated trafficking of proteins in an increasing number of neurodegenerative diseases including
Alzheimer's Disease (AD), Parkinson's Disease (PD) and Frontotemporal Lobar Degeneration
(FTLD). The retromer complex, which is highly conserved across all eukaryotes, regulates the sorting
of transmembrane proteins out of endosomes to the cell surface or to the trans-Golgi network. Within
retromer, cargo selection and binding are performed by a trimer of the Vps26, Vps29 and Vps35 proteins,
named the “Cargo-Selective Complex (CSC)”. Sorting of cargo into tubules for distribution to
the trans-Golgi network or the cell surface is achieved through the dimeric sorting nexin (SNX) component
of retromer and accessory proteins such as the WASH complex which mediates the formation
of discrete endosomal tubules enabling the sorting of cargo into distinct pathways through production
of filamentous actin patches. In the present article, we review the molecular structure and function of
the retromer and summarize the evidence linking retromer dysfunction to neurodegenerative disease.
Keywords: Retromer, Wash complex, Intracellular trafficking, Alzheimer's disease, Genomics, Cell biology.
Rights & PermissionsPrintExport