Retromer Dysfunction and Neurodegenerative Disease.

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.

journal_name

Curr Genomics

journal_title

Current genomics

authors

Reitz C

doi

10.2174/1389202919666171024122809

subject

Has Abstract

pub_date

2018-05-01 00:00:00

pages

279-288

issue

4

eissn

1389-2029

issn

1875-5488

pii

CG-19-279

journal_volume

19

pub_type

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