Exosome Uptake Depends on ERK1/2-Heat Shock Protein 27 Signaling and Lipid Raft-mediated Endocytosis Negatively Regulated by Caveolin-1

Svensson, Katrin J.; Christianson, Helena C.; Wittrup, Anders; Bourseau-Guilmain, Erika; Lindqvist, Eva; Svensson, Lena; Mörgelin, Matthias; Belting, Mattias

doi:10.1074/jbc.m112.445403

Cited by 571 publications

(515 citation statements)

References 40 publications

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“…In prior studies, the mechanism of exosome uptake has varied, and data exists to support each of these pathways (10,12,14,(57)(58)(59)(60). In this study, exosome endocytosis was mediated by dynamin because knockdown or inhibition of this protein attenuated exosome uptake and associated signaling.…”

Section: Discussionmentioning

confidence: 82%

Exosome Adherence and Internalization by Hepatic Stellate Cells Triggers Sphingosine 1-Phosphate-dependent Migration

Wang

Ding

Yaqoob

et al. 2015

Journal of Biological Chemistry

188

172

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Exosomes are cell-derived extracellular vesicles thought to promote intercellular communication by delivering specific content to target cells. The aim of this study was to determine whether endothelial cell (EC)-derived exosomes could regulate the phenotype of hepatic stellate cells (HSCs). Initial microarray studies showed that fibroblast growth factor 2 induced a 2.4-fold increase in mRNA levels of sphingosine kinase 1 (SK1). Exosomes derived from an SK1-overexpressing EC line increased HSC migration 3.2-fold. Migration was not conferred by the dominant negative SK1 exosome. Incubation of HSCs with exosomes was also associated with an 8.3-fold increase in phosphorylation of AKT and 2.5-fold increase in migration. Exosomes were found to express the matrix protein and integrin ligand fibronectin (FN) by Western blot analysis and transmission electron microscopy. Blockade of the FN-integrin interaction with a CD29 neutralizing antibody or the RGD peptide attenuated exosome-induced HSC AKT phosphorylation and migration. Inhibition of endocytosis with transfection of dynamin siRNA, the dominant negative dynamin GTPase construct Dyn2K44A, or the pharmacological inhibitor Dynasore significantly attenuated exosome-induced AKT phosphorylation. SK1 levels were increased in serum exosomes derived from mice with experimental liver fibrosis, and SK1 mRNA levels were up-regulated 2.5-fold in human liver cirrhosis patient samples. Finally, S1PR2 inhibition protected mice from CCl 4 -induced liver fibrosis. Therefore, EC-derived SK1-containing exosomes regulate HSC signaling and migration through FNintegrin-dependent exosome adherence and dynamin-dependent exosome internalization. These findings advance our understanding of EC/HSC cross-talk and identify exosomes as a potential target to attenuate pathobiology signals.

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Section: Discussionmentioning

confidence: 82%

Exosome Adherence and Internalization by Hepatic Stellate Cells Triggers Sphingosine 1-Phosphate-dependent Migration

Wang

Ding

Yaqoob

et al. 2015

Journal of Biological Chemistry

188

172

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“…Recently, phosphatidylserine on the exosome surface is reported to activate macropinocytosis in microglia (21). Svensson et al found that glioblastoma cell-derived exosomes trigger lipid raft-mediated endocytosis through the activation of ERK1/2 signaling pathways that include an important role of heat shock protein 27 (HSP27) (22). Heparan sulfate proteoglycans (HSPGs) were reported to function as receptors of glioblastoma cell-derived exosomes (32).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that exosomes derived from erythroleukemia cells or oligodendroglia cells were internalized through phagocytosis or macropinocytosis, respectively (20,21). Recently, Svensson et al found that glioblastoma cell-derived exosomes were internalized through lipid raft-mediated endocytosis, negatively regulated by caveolin-1 (CAV1) (22). The uptake pathway of exosomes may possibly be cell type specific.…”

mentioning

confidence: 99%

Exosome Uptake through Clathrin-mediated Endocytosis and Macropinocytosis and Mediating miR-21 Delivery

Tian

Zhu

Zhou

et al. 2014

Journal of Biological Chemistry

580

456

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Background: Exosomes can transfer information between cells and facilitate tumor development. Results: PC12 cell-derived exosomes enter into BMSCs through clathrin-mediated endocytosis and macropinocytosis, and decrease the expression of TGF␤RII and TPM1 through miR-21. Conclusion:The results dissect the pathway of exosome internalization and demonstrate their regulation ability. Significance: These findings enhanced our knowledge of the internalization and function of tumor exosomes.

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“…The main indicators of them took part in cell proliferation. The 10 main indicators of 18 main indicators in PC-2 (Table 3), PC-3 (Table 1), and PC-5 (Table 1) (56%) directly were related with MAPK signaling pathway [polyubiquitin , HSP (Svensson et al 2013), MARRS (Wagatsuma and Sakuma 2014), PPI-1 (Zhimin and Hunter 2014), selenium proteins (Bi et al 2016), OSBP (WeberBoyvat et al 2013), PPO, CAT and IAA (Zheng et al 2015), and ABA (Wang et al 2005)]. Therefore, after grafting, callus proliferation may depend on biological responses in MAPK signaling pathway during the camellia shoot graft-healing process.…”

Section: Mapk Signaling Pathway In Callus Proliferation During the Camentioning

confidence: 99%

Signaling pathway in development of Camellia oleifera nurse seedling grafting union

Feng

Yang

Chen

et al. 2017

Trees

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Key message The anatomical and physiological signaling pathways associated with successful scion-rootstock union in nurse seedling grafting of Camellia oleifera propagation are illustrated. Abstract Grafting, the successful union between scion and rootstock, has practical and biological importance. Nurse seedling grafting, as those practiced for Camellia oleifera, often results in high cell division activity and affinity, and is usually associated with significant rootstock and scion anatomical structures changes. However, a comprehensive explanation of signaling pathways, and how they affect graft union development, is still largely unknown. The present study investigates the union formation process in C. oleifera nurse seedling grafts and determines that it consists of six stages, namely, isolation layer formation, rootstock callus differentiation, scion callus differentiation, callus proliferation and connection, cambium differentiation and connection, and conducting tissue differentiation and connection, extending over a period of 35 days. Principal components analyses of the observed changes in physiology and protein expression identified three main factors contributing to the union formation process: cell proliferation, cell differentiation, and vascular bundle development. Further analysis showed that the regulation of the union formation process can be divided into two signaling pathways, namely, calcium and MAPK, which occur during vascular bundle development and cell proliferation and differentiation, respectively.

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Exosome Uptake Depends on ERK1/2-Heat Shock Protein 27 Signaling and Lipid Raft-mediated Endocytosis Negatively Regulated by Caveolin-1

Cited by 571 publications

References 40 publications

Exosome Adherence and Internalization by Hepatic Stellate Cells Triggers Sphingosine 1-Phosphate-dependent Migration

Exosome Adherence and Internalization by Hepatic Stellate Cells Triggers Sphingosine 1-Phosphate-dependent Migration

Exosome Uptake through Clathrin-mediated Endocytosis and Macropinocytosis and Mediating miR-21 Delivery

Signaling pathway in development of Camellia oleifera nurse seedling grafting union

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