Summary of Prof. Yin’s CSEMV-EVCNA award lecture 2021

Abstract

Extracellular vesicles (EVs) have been regarded as influential intracellular delivering parcels that possess tremendous potential because of their strict and complex secretion regulation processes. However, traditional detection methods cannot monitor the secretion of EVs due to their small particle diameters. Inspired by their peculiar diverse appearances and lipid membranes ingredients, we developed an innovative strategy to detect EVs in any kind of fluids by using rationally designed peptide probes that particularly recognize the highly curved surface of EVs. These peptide probes also serve as novel tools to selectively target cancerous cells with specific lipid compositions and distributions. With this strategy, we discovered a series of EV-secreting regulation mechanisms and identified their roles within physiological processes. Recently, we found that the transportation of oligodeoxynucleotides and cell division control protein 42 homolog from TLR9-activated macrophages to naïve cells via EVs exerts synergetic effects in the propagation of the intracellular immune response, which suggests a general mechanism for EV-mediated uptake of pathogen-associated molecular patterns.

Keywords

Extracellular vesicles (EVs) / peptide probe / detection methods

References

[1] Colombo M,Théry C.Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles.Annu Rev Cell Dev Biol2014;30:255-89

[2] Kowal J,Théry C.Biogenesis and secretion of exosomes.Curr Opin Cell Biol2014;29:116-25

[3] Kalluri R.The biology, function and biomedical applications of exosomes.Science2020;367:eaau6977 PMCID:PMC7717626

[4] Andaloussi S, Mäger I, Breakefield XO, Wood MJ. Extracellular vesicles: biology and emerging therapeutic opportunities.Nat Rev Drug Discov2013;12:347-57

[5] Niel G, D'Angelo G, Raposo G. Shedding light on the cell biology of extracellular vesicles.Nat Rev Mol Cell Biol2018;19:213-28

[6] Maas SLN,Weaver AM.Extracellular vesicles: unique intercellular delivery vehicles.Trends Cell Biol2017;27:172-88 PMCID:PMC5318253

[7] Shah R,Freedman JE.Circulating extracellular vesicles in human disease.N Engl J Med2018;379:2179-81

[8] Marar C,Wirtz D.Extracellular vesicles in immunomodulation and tumor progression.Nat Immunol2021;22:560-70

[9] Théry C.Cancer: Diagnosis by extracellular vesicles.Nature2015;523:161-2

[10] Xiao Y,Zhong B.Exosomes as potential sources of biomarkers in colorectal cancer.Cancer Lett2020;476:13-22

[11] Zimmerberg J.Membrane curvature: how BAR domains bend bilayers.Curr Biol2004;14:R250-2

[12] Drin G,Gautier R.A general amphipathic alpha-helical motif for sensing membrane curvature.Nat Struct Mol Biol2007;14:138-46

[13] Saludes JP,Ghosh N.Detection of highly curved membrane surfaces using a cyclic peptide derived from synaptotagmin-I.ACS Chem Biol2012;7:1629-35 PMCID:PMC3477269

[14] Morton LA,Saludes JP.MARCKS-ED peptide as a curvature and lipid sensor.ACS Chem Biol2013;8:218-25 PMCID:PMC3548944

[15] Yan L,Tamura R.Curvature sensing MARCKS-ED peptides bind to membranes in a stereo-independent manner.J Pept Sci2015;21:577-85 PMCID:PMC4480065

[16] Saludes JP,Coulup SK.Multivalency amplifies the selection and affinity of bradykinin-derived peptides for lipid nanovesicles.Mol Biosyst2013;9:2005-9 PMCID:PMC3764994

[17] Bonechi C,Martini G,Rossi C.Study of bradykinin conformation in the presence of model membrane by Nuclear Magnetic Resonance and molecular modelling.Biochim Biophys Acta2009;1788:708-16

[18] Langelaan DN.Membrane catalysis of peptide-receptor binding.Biochem Cell Biol2010;88:203-10 PMCID:PMC3024292

[19] Chatterjee C.Conformational alteration of bradykinin in presence of GM1 micelle.Biochem Biophys Res Commun2004;315:866-71

[20] Février B.Exosomes: endosomal-derived vesicles shipping extracellular messages.Curr Opin Cell Biol2004;16:415-21

[21] Subra C,Perret B.Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies.Biochimie2007;89:205-12

[22] Zhang Y,Liang J.Extracellular vesicles derived from ODN-stimulated macrophages transfer and activate Cdc42 in recipient cells and thereby increase cellular permissiveness to EV uptake.Sci Adv2019;5:eaav1564 PMCID:PMC6656539

[23] Zhang Y,Sun G.Harnessing the therapeutic potential of extracellular vesicles for cancer treatment.Semin Cancer Biol2021;74:92-104