Systematic Analysis of GARP- and EARP-Mediated Trafficking Pathways Using Lysosomal Proteomics
Year: 2026
Type: preprint
Abstract: Eukaryotic cells utilize tethering complexes for sorting of proteins within the endo-lysosomal system. The GARP complex and the EARP complex both function in endosomal recycling. Both complexes share three common subunits (VPS51, VPS52, and VPS53), with each relying on one specific subunit: VPS54 for GARP and VPS50 for EARP. Mutations in both complexes are linked to various neurodegenerative disorders. While model cargoes have been described, the cargo spectrum of both complexes remains largely elusive. Here, we combined lysosomal proteomics with knockdowns of GARP and EARP to analyze their cargo spectra. Using the lysosome as a terminal reference point for mis-sorted proteins, we show that GARP depletion causes a loss in lysosomal hydrolases and accumulation of non-lysosomal cargo. EARP depletion results in lysosomal accumulation of secreted proteins. Our findings serve as a reference to study GARP and EARP complexes. We demonstrate that a systematic phenotypic analysis of GARP and EARP mutants is necessary to understand the pathological consequences of their dysfunction.
Institution: Osnabrück University
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
Awards: Molekulare Mechanismen der SphingolipidHomöostase und ihre Auswirkung auf die Zellphysiologie, Entschlüsselung der endosomalen Recyclingwege: Einblicke in die Protein und Lipidsortierung im endolysosomalen System, SFB 1557: Funktionelle Plastizität, kodiert durch zellulare Membrannetzwerke, G6625650684, ESIIMMassenspektrometer, Massenspektrometrie, quantitative Lipidanalysen und Lipidwerkzeuge, Molekulare Analyse der Sphingolipid und Sterolhomöostase in Hefe
OpenAlex ID: W7221192430