LAMP2A regulates the loading of proteins into exosomes-Reference-Cited by-同舟云学术

LAMP2A regulates the loading of proteins into exosomes

Published:2022-03-25 Issue:12 Volume:8 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Ferreira João Vasco¹^ORCID,da Rosa Soares Ana¹^ORCID,Ramalho José¹^ORCID,Máximo Carvalho Catarina¹^ORCID,Cardoso Maria Helena¹^ORCID,Pintado Petra²^ORCID,Carvalho Ana Sofia³^ORCID,Beck Hans Christian⁴,Matthiesen Rune³^ORCID,Zuzarte Mónica⁵^ORCID,Girão Henrique⁵,van Niel Guillaume⁶⁷^ORCID,Pereira Paulo¹^ORCID

Affiliation:

1. Proteostasis and Proteolytic Signalling Lab, Chronic Diseases Research Centre (CEDOC), NOVA Medical School, Faculdade de Ciencias Medicas, Universidade NOVA de Lisboa, Lisbon, Portugal.

2. Fish Facility, CEDOC, NOVA Medical School, Faculdade de Ciencias Medicas, Universidade NOVA de Lisboa, Lisbon, Portugal.

3. Computational and Experimental Biology Group, CEDOC, NOVA Medical School, Faculdade de Ciencias Medicas, Universidade NOVA de Lisboa, Lisbon, Portugal.

4. Centre for Clinical Proteomics, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.

5. University of Coimbra, Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, Center for Innovative Biomedicine and Biotechnology (CIBB), Clinical Academic Centre of Coimbra (CACC), Coimbra, Portugal.

6. Université de Paris, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, F-75014 Paris, France.

7. GHU Paris Psychiatrie et Neurosciences, Hôpital Sainte Anne, F-75014 Paris, France.

Abstract

Exosomes are extracellular vesicles of endosomal origin that are released by practically all cell types across metazoans. Exosomes are active vehicles of intercellular communication and can transfer lipids, RNAs, and proteins between different cells, tissues, or organs. Here, we describe a mechanism whereby proteins containing a KFERQ motif pentapeptide are loaded into a subpopulation of exosomes in a process that is dependent on the membrane protein LAMP2A. Moreover, we demonstrate that this mechanism is independent of the ESCRT machinery but dependent on HSC70, CD63, Alix, Syntenin-1, Rab31, and ceramides. We show that the master regulator of hypoxia HIF1A is loaded into exosomes by this mechanism to transport hypoxia signaling to normoxic cells. In addition, by tagging fluorescent proteins with KFERQ-like sequences, we were able to follow the interorgan transfer of exosomes. Our findings open new avenues for exosome engineering by allowing the loading of bioactive proteins by tagging them with KFERQ-like motifs.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference57 articles.

1. Shedding light on the cell biology of extracellular vesicles

2. Extracellular vesicles shuffling intercellular messages: for good or for bad

3. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes

4. The biology , function , and biomedical applications of exosomes

5. Biogenesis, Secretion, and Intercellular Interactions of Exosomes and Other Extracellular Vesicles

Cited by 64 articles. 订阅此论文施引文献订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献

1. The ins-and-outs of exosome biogenesis, secretion, and internalization;Trends in Cell Biology;2024-02

2. Roles of exosomes in immunotherapy for solid cancers;Cell Death & Disease;2024-02-01

3. Extracellular vesicles as therapeutics for inflammation and infection;Current Opinion in Biotechnology;2024-02

4. Recent advances of vacuolar protein-sorting 34 inhibitors targeting autophagy;Bioorganic Chemistry;2024-02

5. Exosomal secreted SCIMP regulates communication between macrophages and neutrophils in pneumonia;Nature Communications;2024-01-23