Retromer Dysfunction and Neurodegenerative Disease

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.

• Publication year

  2017

• Venue

  Current Genomics

• Publication date

  2017-10-24

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.2174/1389202919666171024122809PMID 29755290PMCID 5930449
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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