Retromer Dysfunction and Neurodegenerative Disease

Current Genomics
Christiane Reitz

Abstract

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 Degener-ation (FTLD). The retromer complex, which is highly conserved across all eukaryotes, regulates the sorting of transmembrane proteins out of endo-somes 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 sur-face is achieved through the dimeric sorting nexin (SNX) component of retromer and accessory proteins such as the WASH complex which medi-ates the formation of discrete endosomal tubules enabling the sorting of cargo into distinct pathways through production of filamentous actin patch-es. In the present article, we review the molecular structure and function of the retromer and summarize the evidence linking retromer dysfunction to neurodegenerative disease.

Citations

Jul 25, 2019·Cells·José Ángel Martínez-MenárguezEmma Martínez-Alonso
Nov 9, 2018·Frontiers in Synaptic Neuroscience·Lennart Brodin, Oleg Shupliakov
Oct 8, 2020·Nature Communications·Harriet Crawley-SnowdonDavid J Owen
Dec 31, 2020·Proceedings of the National Academy of Sciences of the United States of America·Zhike FengPeter D Nagy
Oct 31, 2020·Biochemical Society Transactions·Mintu ChandraLauren P Jackson
Oct 19, 2021·Frontiers in Genetics·Chia-Hsiang ChenLieh-Yung Ping
Jan 14, 2022·Proceedings of the National Academy of Sciences of the United States of America·Bo YangGuijun Shang

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Datasets Mentioned

BETA
KIAA1033

Methods Mentioned

BETA
GTPases
nucleotide
GTPase

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