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Autophagy. 2021 Nov;17(11):3865-3874. doi: 10.1080/15548627.2021.1876343. Epub 2021 Jan 26.

Quantitative proteomic analysis of temporal lysosomal proteome and the impact of the KFERQ-like motif and LAMP2A in lysosomal targeting.

Autophagy

Merve Kacal, Boxi Zhang, Yuqing Hao, Erik Norberg, Helin Vakifahmetoglu-Norberg

Affiliations

  1. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.

PMID: 33446043 PMCID: PMC8632328 DOI: 10.1080/15548627.2021.1876343

Abstract

Autophagic pathways are regulated mechanisms that play important roles in lysosome-mediated cellular degradation. Yet, the contribution of different autophagic pathways in lysosomal targeting, and characterization of the extent and specificity in their degradome remains largely uncharacterized. By undertaking a multiplex quantitative mass spectrometry approach, we have previously analyzed the lysosomal proteome during chaperone-mediated autophagy (CMA)-stimulated conditions in cancer cells. Here, we have extended our multiplex quantitative mass spectrometry and bioinformatics analysis on the proteome from isolated lysosomes to gain a comprehensive view of the temporal enriched lysosomal content upon non-macroautophagy-activated conditions. In parallel, we describe the functional dependency of LAMP2A on, and to what degree the presence of KFERQ-like motifs in proteins influences, their lysosomal targeting. These findings establish a framework for a better understanding of the degradome mediated by autophagic pathways beyond macroautophagy, and present characterization of the impact of LAMP2A in lysosomal targeting in cancer cells.

Keywords: Autophagy; cancer; chaperone-mediated autophagy; lysosome; proteomics

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