title: Retromer's Role in Endosomal Trafficking and Impaired Function in Neurodegenerative Diseases.
abstract: The retromer complex is a highly conserved membrane trafficking assembly composed of three proteins - Vps26, Vps29 and Vps35 - that were identified over a decade ago in Saccharomyces cerevisiae (S. cerevisiae). Initially, mammalian retromer was shown to sort transmembrane proteins from the endosome to the trans-Golgi network (TGN), though recent work has identified a critical role for retromer in multiple trafficking pathways, including recycling to the plasma membrane and regulation of cell polarity. In recent years, genetic, cellular, pharmacological and animal model studies have identified retromer and its interacting proteins as being linked to familial forms of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). Here, this commentary will summarize recently identified point mutations in retromer linked to PD, and explore the molecular functions of retromer that may be relevant to disease progression.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland. Australia.
authors.forename: Jordan
authors.initials: J
authors.lastname: Follett
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland. Australia.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bugarcic
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland. Australia.
authors.forename: Brett M
authors.initials: BM
authors.lastname: Collins
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072. Australia.
authors.forename: Rohan D
authors.initials: RD
authors.lastname: Teasdale
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002402:Cathepsin D / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D009154:Mutation; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: C498296:VPS26A protein, human; C419572:VPS29 protein, human; C419573:VPS35 protein, human; D033921:Vesicular Transport Proteins; C533922:CTSD protein, human; D002402:Cathepsin D
keywords: Cathepsin D; Parkinson's disease; Vps35 p.D620N; Vps35 p.R524W; endosome; retromer; sorting nexin