title: Retromer Ensures the Degradation of Autophagic Cargo by Maintaining Lysosome Function in Drosophila.
abstract: The retromer is an evolutionarily conserved coat complex that consists of Vps26, Vps29, Vps35 and a heterodimer of sorting nexin (Snx) proteins in yeast. Retromer mediates the recycling of transmembrane proteins from endosomes to the trans-Golgi network, including receptors that are essential for the delivery of hydrolytic enzymes to lysosomes. Besides its function in lysosomal enzyme receptor recycling, involvement of retromer has also been proposed in a variety of vesicular trafficking events, including early steps of autophagy and endocytosis. Here we show that the late stages of autophagy and endocytosis are impaired in Vps26 and Vps35 deficient Drosophila larval fat body cells, but formation of autophagosomes and endosomes is not compromised. Accumulation of aberrant autolysosomes and amphisomes in the absence of retromer function appears to be the consequence of decreased degradative capacity, as they contain undigested cytoplasmic material. Accordingly, we show that retromer is required for proper cathepsin L trafficking mainly independent of LERP, the Drosophila homolog of the cation-independent mannose 6-phosphate receptor. Finally, we find that Snx3 and Snx6 are also required for proper autolysosomal degradation in Drosophila larval fat body cells.
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pázmány Péter sétány 1./C, Budapest, H-1117, Hungary.|Momentum Drosophila Autophagy Research Group, Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary.
authors.forename: Tamás
authors.identifier: http://orcid.org/0000-0001-8142-3221
authors.initials: T
authors.lastname: Maruzs
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pázmány Péter sétány 1./C, Budapest, H-1117, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Lőrincz
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pázmány Péter sétány 1./C, Budapest, H-1117, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Szatmári
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pázmány Péter sétány 1./C, Budapest, H-1117, Hungary.
authors.forename: Szilvia
authors.initials: S
authors.lastname: Széplaki
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pázmány Péter sétány 1./C, Budapest, H-1117, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Sándor
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pázmány Péter sétány 1./C, Budapest, H-1117, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Lakatos
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pázmány Péter sétány 1./C, Budapest, H-1117, Hungary.
authors.forename: Gina
authors.initials: G
authors.lastname: Puska
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pázmány Péter sétány 1./C, Budapest, H-1117, Hungary.|Momentum Drosophila Autophagy Research Group, Institute of Genetics, Biological Research Centre, Hungarian Academy of Sciences, Temesvári krt. 62, Szeged, H-6726, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Juhász
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Pázmány Péter sétány 1./C, Budapest, H-1117, Hungary.
authors.forename: Miklós
authors.initials: M
authors.lastname: Sass
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism / Q000502:physiology; D004330:Drosophila / Q000378:metabolism* / Q000502:physiology; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism / Q000502:physiology; D005216:Fat Body / Q000378:metabolism / Q000502:physiology; D008247:Lysosomes / Q000378:metabolism* / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D058305:Sorting Nexins / Q000378:metabolism*; D014617:Vacuoles / Q000378:metabolism / Q000502:physiology; D033921:Vesicular Transport Proteins / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins
keywords: Drosophila; autophagy; endocytosis; lysosomal storage diseases; lysosome; retromer