Journal
AUTOPHAGY
Volume 18, Issue 9, Pages 2263-2265Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2022.2092315
Keywords
eLLoC; LAMP2A; exosomes; intercellular communication; inter-organ communication; chaperones; autophagy; endosomes; lysosome
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Funding
- Portuguese Foundation for Science and Technology [SFRH/BPD/121271/2016, PD/BD/106052/2015, 02/SAICT/2020/072552, UIDB/04462/2020, UIDP/04462/2020]
- Fundacao para a Ciencia e Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior [LA/P/0087/2020]
- Fundação para a Ciência e a Tecnologia [PD/BD/106052/2015, SFRH/BPD/121271/2016] Funding Source: FCT
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Exosomes, a subtype of extracellular vesicles, play important roles in health and disease by transporting biological information. The mechanisms of protein loading into exosomes are not well understood, but recent research has identified a process mediated by LAMP2A. This process shows similarities to chaperone-mediated autophagy and endosomal microautophagy.
Exosomes are a subtype of extracellular vesicles (EVs), released by all cell types, that originate from the invagination of the endosomal limiting membrane. These EVs can transport biological information in the form of proteins and RNA and have been the focus of intensive research over the last decade. It is becoming apparent that EVs can have important roles in health and disease. EVs are also promising noninvasive biomarkers of disease (liquid biopsies) and valuable vectors for innovative therapies. However, little is known about the mechanisms that regulate the loading of cytosolic proteins into exosomes. We recently showed that soluble proteins containing amino acid sequences biochemically related to the KFERQ motif are loaded into nascent exosomes at the endosomal limiting membrane, in a process mediated by LAMP2A. Because of the subcellular localization and machinery involved, this mechanism has many similarities with chaperone-mediated autophagy (CMA) and endosomal microautophagy (e-Mi), but also some important differences. In this punctum we will focus on the mechanistic details of exosomal LAMP2A loading of cargo (e-LLoC) as well as on its implications for intercellular and interorgan communication.
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