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TRX2/Rab35 Interaction Impairs Exosome Secretion by Inducing Rab35 Degradation

Given that exosomes mediate intercellular communication by delivering cellular components to recipient cells or tissue, they have the potential to be engineered to deliver therapeutic payloads. However, the regulatory mechanism of exosome secretion is poorly understood. In addition, mitochondrial co...

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Detalles Bibliográficos
Autores principales: Zhang, Tao, Zhao, Lili, Han, Liping, Li, Yan, Hu, Lanlin, Wang, Huani, Zou, Fangdong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224307/
https://www.ncbi.nlm.nih.gov/pubmed/35743001
http://dx.doi.org/10.3390/ijms23126557
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author Zhang, Tao
Zhao, Lili
Han, Liping
Li, Yan
Hu, Lanlin
Wang, Huani
Zou, Fangdong
author_facet Zhang, Tao
Zhao, Lili
Han, Liping
Li, Yan
Hu, Lanlin
Wang, Huani
Zou, Fangdong
author_sort Zhang, Tao
collection PubMed
description Given that exosomes mediate intercellular communication by delivering cellular components to recipient cells or tissue, they have the potential to be engineered to deliver therapeutic payloads. However, the regulatory mechanism of exosome secretion is poorly understood. In addition, mitochondrial components have been found in exosomes, suggesting communication between mitochondria and exosomes. However, the molecular mechanism of the mitochondria and vesicle interaction remains unclear. Here, we showed that mitochondrial thioredoxin 2 (TRX2) decreased exosome concentrations and inhibited HCT116 cell migration. Coimmunoprecipitation/mass spectrometry (Co-IP/MS) showed that TRX2 interacted with Rab35. TRX2 and Rab35 bound to each other at their N-terminal motifs and colocalized on mitochondria. Furthermore, TRX2 induced Rab35 degradation, resulting in impaired exosome secretion. Additionally, Rab35 mediated the suppressive effects of TRX2 on cell migration, and TRX2 suppressed cell migration through exosomes. Taken together, this study first found an interaction between TRX2 and Rab35. These results revealed a new role for TRX2 in the regulation of exosome secretion and cell migration and explained the upstream regulatory mechanism of Rab35. Furthermore, these findings also provide new molecular evidence for communication between mitochondria and vesicles.
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spelling pubmed-92243072022-06-24 TRX2/Rab35 Interaction Impairs Exosome Secretion by Inducing Rab35 Degradation Zhang, Tao Zhao, Lili Han, Liping Li, Yan Hu, Lanlin Wang, Huani Zou, Fangdong Int J Mol Sci Article Given that exosomes mediate intercellular communication by delivering cellular components to recipient cells or tissue, they have the potential to be engineered to deliver therapeutic payloads. However, the regulatory mechanism of exosome secretion is poorly understood. In addition, mitochondrial components have been found in exosomes, suggesting communication between mitochondria and exosomes. However, the molecular mechanism of the mitochondria and vesicle interaction remains unclear. Here, we showed that mitochondrial thioredoxin 2 (TRX2) decreased exosome concentrations and inhibited HCT116 cell migration. Coimmunoprecipitation/mass spectrometry (Co-IP/MS) showed that TRX2 interacted with Rab35. TRX2 and Rab35 bound to each other at their N-terminal motifs and colocalized on mitochondria. Furthermore, TRX2 induced Rab35 degradation, resulting in impaired exosome secretion. Additionally, Rab35 mediated the suppressive effects of TRX2 on cell migration, and TRX2 suppressed cell migration through exosomes. Taken together, this study first found an interaction between TRX2 and Rab35. These results revealed a new role for TRX2 in the regulation of exosome secretion and cell migration and explained the upstream regulatory mechanism of Rab35. Furthermore, these findings also provide new molecular evidence for communication between mitochondria and vesicles. MDPI 2022-06-12 /pmc/articles/PMC9224307/ /pubmed/35743001 http://dx.doi.org/10.3390/ijms23126557 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Tao
Zhao, Lili
Han, Liping
Li, Yan
Hu, Lanlin
Wang, Huani
Zou, Fangdong
TRX2/Rab35 Interaction Impairs Exosome Secretion by Inducing Rab35 Degradation
title TRX2/Rab35 Interaction Impairs Exosome Secretion by Inducing Rab35 Degradation
title_full TRX2/Rab35 Interaction Impairs Exosome Secretion by Inducing Rab35 Degradation
title_fullStr TRX2/Rab35 Interaction Impairs Exosome Secretion by Inducing Rab35 Degradation
title_full_unstemmed TRX2/Rab35 Interaction Impairs Exosome Secretion by Inducing Rab35 Degradation
title_short TRX2/Rab35 Interaction Impairs Exosome Secretion by Inducing Rab35 Degradation
title_sort trx2/rab35 interaction impairs exosome secretion by inducing rab35 degradation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224307/
https://www.ncbi.nlm.nih.gov/pubmed/35743001
http://dx.doi.org/10.3390/ijms23126557
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