RRC ID 34904
Author Maruzs T, Lőrincz P, Szatmári Z, Széplaki S, Sándor Z, Lakatos Z, Puska G, Juhász G, Sass M.
Title Retromer Ensures the Degradation of Autophagic Cargo by Maintaining Lysosome Function in Drosophila.
Journal Traffic
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.
Volume 16(10)
Pages 1088-107
Published 2015-10
DOI 10.1111/tra.12309
PMID 26172538
MeSH Animals Autophagy / physiology* Carrier Proteins / metabolism Cytoplasm / metabolism Cytoplasm / physiology Drosophila / metabolism* Drosophila / physiology Endocytosis / physiology Endosomes / metabolism Endosomes / physiology Fat Body / metabolism Fat Body / physiology Lysosomes / metabolism* Lysosomes / physiology Protein Transport / physiology Sorting Nexins / metabolism* Vacuoles / metabolism Vacuoles / physiology Vesicular Transport Proteins / metabolism trans-Golgi Network / metabolism trans-Golgi Network / physiology
IF 3.951
Times Cited 4
Drosophila 2774R-1 6359R-1 8282R-2 5625R-3