外泌体与自噬体相互关系研究进展
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摘要
真核细胞内膜系统由细胞内相互联系的膜状细胞器组成,包括外泌体的生成和自噬过程,对应激反应和维持细胞内稳态起着重要作用。外泌体是含有蛋白质与核酸内容物的多泡体分泌到体外形成的胞外囊泡,而自噬是溶酶体依赖性的降解和循环再利用的过程。研究发现,外泌体的生成和自噬之间有着共同的分子机制,二者存在实质性的交互通信。对外泌体的生成和自噬的过程,包括二者与溶酶体之间的关系进行综述。
The eukaryotic intima system consists of intercellular membranous organelles,including the formation of exosomes and autophagy,which play an important role in stress response and maintenance of cell homeostasis. Exosomes are extracellular vesicles secreted into the body by multivesicular bodies containing contents of proteins and nuclear acids,while autophagy is a process of lysosomal-dependent degradation and recycling. There is a common molecular mechanism between the formation of exosomes and autophagy,and substantial interaction between them were founded. The formation of exosomes and the process of autophagy was reviewed,including the relationship between the two and lysosomes.
The eukaryotic intima system consists of intercellular membranous organelles,including the formation of exosomes and autophagy,which play an important role in stress response and maintenance of cell homeostasis. Exosomes are extracellular vesicles secreted into the body by multivesicular bodies containing contents of proteins and nuclear acids,while autophagy is a process of lysosomal-dependent degradation and recycling. There is a common molecular mechanism between the formation of exosomes and autophagy,and substantial interaction between them were founded. The formation of exosomes and the process of autophagy was reviewed,including the relationship between the two and lysosomes.
引文
[1]Pan B T,Johnstone R M. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro:selective externalization of the receptor. Cell,1983,33(3):967-978.
[2]Claude-Taupin A,Jia J,Mudd M,et al. Autophagy’s secret life:secretion instead of degradation. Essays Biochem,2017,61(6):637-647.
[3] Cadwell K, Debnath J. Beyond self-eating:the control of nonautophagic functions and signaling pathways by autophagyrelated proteins. J Cell Biol,2018,217(3):813-822.
[4] Baixauli F, López-Otin C, Mittelbrunn M. Exosomes and autophagy:coordinated mechanisms for the maintenance of cellular fitness. Front Immunol,2014,5:403.
[5] Ojha C R,Lapierre J,Rodriguez M,et al. Interplay between autophagy, exosomes and HIV-1 associated neurological disorders:new insights for diagnosis and therapeutic applications.Viruses,2017,9(7):176.
[6] Scott C C,Vacca F,Gruenberg J. Endosome maturation,transport and functions. Semin Cell Dev Biol,2014,31:2-10.
[7]Hessvik N P,Llorente A. Current knowledge on exosome biogenesis and release. Cell Mol Life Sci,2018,75(2):193-208.
[8] Yez-MóM,Siljander P R,Andreu Z,et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles,2015,4(1):27066.
[9]Hurley J H. ESCRTs are everywhere. EMBO J,2015,34(19):2398-2407.
[10] Colombo M,Moita C,van Niel G,et al. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J Cell Sci,2013,126(Pt 24):5553-5565.
[11]Trajkovic K,Hsu C,Chiantia S,et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science,2008,319(5867):1244-1247.
[12]Xu J,Camfield R,Gorski S M. The interplay between exosomes and autoph-agy-partners in crime. J Cell Sci,2018,131(15):215210.
[13] Villarroya-Beltri C,Baixauli F,Gutiérrez-Vzquez C,et al.Sorting it out:regulation of exosome loading. Semin Cancer Biol,2014,28:3-13.
[14]Janas T,Janas M,Sapon'K,et al. Mechanisms of RNA loading into exosomes. FEBS Lett,2015,89(13):1391-1398.
[15] Andreu Z,Yez-MóM. Tetraspanins in extracellular vesicle formation and function. Front Immunol,2014,5:442.
[16] Smith V L, Jackson L, Schorey J S. Ubiquitination as a mechanism to transport soluble mycobacterial and eukaryotic proteins to exosomes. J Immunol,2015,195(6):2722-2730.
[17] Sahu R,Kaushik S,Clement C C,et al. Microautophagy of cytosolic proteins by late endosomes. Dev Cell,2011,20(1):131-139.
[18] Edgar J R,Manna P T,Nishimura S,et al. Tetherin is an exosomal tether. e Life,2016,5:e17180.
[19] Hoshino A,Costa-Silva B,Shen T L,et al. Tumour exosome integrins determine organotropic metastasis. Nature,2015,527(7578):329-335.
[20]Kamerkar S,Lebleu V S,Sugimoto H,et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer.Nature,2017,546(7659):498-503.
[21] Christianson H C,Svensson K J,Van Kuppevelt T H,et al.Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. Proc Natl Acad Sci USA,2013,110(43):17380-17385.
[22] Mulcahy L A,Pink R C,Carter D R. Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles,2014,3(1):24641.
[23] Heusermann W,Hean J,Trojer D,et al. Exosomes surf on filopodia to enter cells at endocytic hot spots, traffic within endosomes,and are targeted to the ER. J Cell Biol,2016,213(2):173-184.
[24]Klionsky D J,Emr S D. Autophagy as a regulated pathway of cellular degradation. Science,2000,290(5497):1717-1721.
[25] Galluzzi L,Baehrecke E H,Ballabio A,et al. Molecular definitions of autophagy and related processes. EMBO J,2017,36(13):1811-1836.
[26] Tsukada M, Ohsumi Y. Isolation and characterization of autophagydefective mutants of saccharomyces cerevisiae. FEBS Lett,1993,333(1-2):169-174.
[27]Park J M,Jung C H,Seo M,et al. The ULK1 complex mediates MTORC1 signaling to the autophagy initiation machinery via binding and phosphorylating ATG14. Autophagy,2016,12(3):547-564.
[28]Matsuura A,Tsukada M,Wada Y,et al. Apg1p,a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae. Gene,1997,192(2):245-250.
[29] Ichimura Y,Kirisako T,Takao T,et al. A ubiquitinlike system mediates protein lipidation. Nature,2000,408(6811):488-492.
[30]Zhang M,Kenny S J,Ge L,et al. Translocation of interleukin-1βinto a vesicle intermediate in autophagy-mediated secretion.e Life,2015,4:1463.
[31] Deretic V,Jiang S,Dupont N. Autophagy intersections with conventional and unconventional secretion in tissue development,remodeling and inflammation. Trends Cell Biol,2012,22(8):397-406.
[32]Florey O,Kim S E,Sandoval C P,et al. Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranes. Nat Cell Biol,2011,13(11):1335-1343.
[33] Martinez J, Almendinger J, Oberst A, et al Microtubuleassociated protein 1 light chain 3 alpha(LC3)-associated phagocytosis is required for the efficient clearance of dead cells.Proc Natl Acad Sci USA,2011,108(42):17396-17401.
[34]Fletcher K,Ulferts R,Jacquin E,et al. The WD40 domain of ATG16L1 is required for its non-canonical role in lipidation of LC3 at single membranes. EMBO J,2018,37(4):e97840.
[35]Codogno P,Mehrpour M,Proikas-Cezanne T. Canonical and noncanonical autophagy:variations on a common theme of selfeating. Nat Rev Mol Cell Biol,2011,13(1):7-12.
[36]Jacquin E,Leclerc-Mercier S,Judon C,et al. Pharmacological modulators of autophagy activate a parallel noncanonical pathway driving unconventional LC3 lipidation. Autophagy,2017,13(5):854-867.
[37] Tooze S A,Abada A,Elazar Z. Endocytosis and autophagy:exploitation or cooperation. Cold Spring Harbor Perspect Biol,2014,6(5):a018358.
[38]Guo H,Chitiprolu M,Roncevic L,et al. Atg5 disassociates the V1V0-ATPase to promote exosome production and tumor metastasis independent of canonical macroautophagy. Dev Cell,2017,43(6):716-730.
[39]Murrow L,Malhotra R,Debnath J. ATG12-ATG3 interacts with Alix to promote basal autophagic flux and late endosome function.Nat Cell Biol,2015,17(3):300-310.
[40] Martinez J, Malireddi R K, Lu Q, et al. Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon,NOX2 and autophagy proteins. Nat Cell Biol,2015,17(7):893-906.
[41] Liu J,Zhang Y,Liu A,et al. Distinct dasatinib-induced mechanisms of apoptotic response and exosome release in imatinibresistant human chronic myeloid leukemia cells. Int J Mol Sci,2016,17(4):531.
[42] Bader CA,Shandala T,Ng Y S,et al. Atg9 is required for intraluminal vesicles in amphisomes and autolysosomes. Biol Open,2015,4(11):1345-1355.
[43]Liou W,Geuze H J,Geelen M J,et al. The autophagic and endocytic pathways converge at the nascent autophagic vacuoles. J Cell Biol,1997,136(1):61-70.
[44]Fade C M,Snchez D,Furln M,et al. Induction of autophagy promotes fusion of multivesicular bodies with autophagic vacuoles in k562 cells. Traffic,2008,9(2):230-250.
[45]Villarroya-Beltri C,Baixauli F,Mittelbrunn M,et al. ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins. Nat Commun,2016,7:13588.
[46] Hurwitz S N,Cheerathodi M R,Nkosi D,et al. Tetraspanin CD63 bridges autophagic and endosomal processes to regulate exosomal secretion and intracellular signaling of Epstein-Barr virus LMP1. J Virol,2018,92(5):e01969-17.
[47] Patel K K,Miyoshi H,Beatty W L,et al. Autophagy proteins control goblet cell function by potentiating reactive oxygen species production. EMBO J,2013,32(4):3130-3144.
[48]Chen Y D,Fang Y T,Cheng Y L,et al. Exophagy of annexin A2via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells. Sci Rep,2017,7(1):5676.
[49]Bukong T N,Momen-Heravi F,Kodys K,et al. Exosomes from hepatitis C infected patients transmit HCV infection and contain replication competent viral RNA in complex with Ago2-miR122-HSP90. PLo S Pathog,2014,10(10):e1004424.
[50] Liu Z,Zhang X,Yu Q,et al. Exosome-associated hepatitis C virus in cell cultures and patient plasma. Biochem Biophys Res Commun,2014,455(3-4):218-222.
[51]Shrivastava S,Devhare P,Sujijantarat N,et al. Knockdown of autophagy inhibits infectious hepatitis C virus release by the exosomal pathway. J Virol,2015,90(3):1387-1396.
[52] Ren H,Elgner F,Jiang B,et al. The autophagosomal SNARE protein syntaxin 17 is an essential factor for the hepatitis C virus life cycle. J Virol,2016,90(13):5989-6000.
[53]Wang L,Tian Y,Ou J J,et al. HCV induces the expression of Rubicon and UVRAG to temporally regulate the maturation of autophagosomes and viral replication. PLo S Pathog,2015,11(3):e1004764.
[2]Claude-Taupin A,Jia J,Mudd M,et al. Autophagy’s secret life:secretion instead of degradation. Essays Biochem,2017,61(6):637-647.
[3] Cadwell K, Debnath J. Beyond self-eating:the control of nonautophagic functions and signaling pathways by autophagyrelated proteins. J Cell Biol,2018,217(3):813-822.
[4] Baixauli F, López-Otin C, Mittelbrunn M. Exosomes and autophagy:coordinated mechanisms for the maintenance of cellular fitness. Front Immunol,2014,5:403.
[5] Ojha C R,Lapierre J,Rodriguez M,et al. Interplay between autophagy, exosomes and HIV-1 associated neurological disorders:new insights for diagnosis and therapeutic applications.Viruses,2017,9(7):176.
[6] Scott C C,Vacca F,Gruenberg J. Endosome maturation,transport and functions. Semin Cell Dev Biol,2014,31:2-10.
[7]Hessvik N P,Llorente A. Current knowledge on exosome biogenesis and release. Cell Mol Life Sci,2018,75(2):193-208.
[8] Yez-MóM,Siljander P R,Andreu Z,et al. Biological properties of extracellular vesicles and their physiological functions. J Extracell Vesicles,2015,4(1):27066.
[9]Hurley J H. ESCRTs are everywhere. EMBO J,2015,34(19):2398-2407.
[10] Colombo M,Moita C,van Niel G,et al. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J Cell Sci,2013,126(Pt 24):5553-5565.
[11]Trajkovic K,Hsu C,Chiantia S,et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science,2008,319(5867):1244-1247.
[12]Xu J,Camfield R,Gorski S M. The interplay between exosomes and autoph-agy-partners in crime. J Cell Sci,2018,131(15):215210.
[13] Villarroya-Beltri C,Baixauli F,Gutiérrez-Vzquez C,et al.Sorting it out:regulation of exosome loading. Semin Cancer Biol,2014,28:3-13.
[14]Janas T,Janas M,Sapon'K,et al. Mechanisms of RNA loading into exosomes. FEBS Lett,2015,89(13):1391-1398.
[15] Andreu Z,Yez-MóM. Tetraspanins in extracellular vesicle formation and function. Front Immunol,2014,5:442.
[16] Smith V L, Jackson L, Schorey J S. Ubiquitination as a mechanism to transport soluble mycobacterial and eukaryotic proteins to exosomes. J Immunol,2015,195(6):2722-2730.
[17] Sahu R,Kaushik S,Clement C C,et al. Microautophagy of cytosolic proteins by late endosomes. Dev Cell,2011,20(1):131-139.
[18] Edgar J R,Manna P T,Nishimura S,et al. Tetherin is an exosomal tether. e Life,2016,5:e17180.
[19] Hoshino A,Costa-Silva B,Shen T L,et al. Tumour exosome integrins determine organotropic metastasis. Nature,2015,527(7578):329-335.
[20]Kamerkar S,Lebleu V S,Sugimoto H,et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer.Nature,2017,546(7659):498-503.
[21] Christianson H C,Svensson K J,Van Kuppevelt T H,et al.Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. Proc Natl Acad Sci USA,2013,110(43):17380-17385.
[22] Mulcahy L A,Pink R C,Carter D R. Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles,2014,3(1):24641.
[23] Heusermann W,Hean J,Trojer D,et al. Exosomes surf on filopodia to enter cells at endocytic hot spots, traffic within endosomes,and are targeted to the ER. J Cell Biol,2016,213(2):173-184.
[24]Klionsky D J,Emr S D. Autophagy as a regulated pathway of cellular degradation. Science,2000,290(5497):1717-1721.
[25] Galluzzi L,Baehrecke E H,Ballabio A,et al. Molecular definitions of autophagy and related processes. EMBO J,2017,36(13):1811-1836.
[26] Tsukada M, Ohsumi Y. Isolation and characterization of autophagydefective mutants of saccharomyces cerevisiae. FEBS Lett,1993,333(1-2):169-174.
[27]Park J M,Jung C H,Seo M,et al. The ULK1 complex mediates MTORC1 signaling to the autophagy initiation machinery via binding and phosphorylating ATG14. Autophagy,2016,12(3):547-564.
[28]Matsuura A,Tsukada M,Wada Y,et al. Apg1p,a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae. Gene,1997,192(2):245-250.
[29] Ichimura Y,Kirisako T,Takao T,et al. A ubiquitinlike system mediates protein lipidation. Nature,2000,408(6811):488-492.
[30]Zhang M,Kenny S J,Ge L,et al. Translocation of interleukin-1βinto a vesicle intermediate in autophagy-mediated secretion.e Life,2015,4:1463.
[31] Deretic V,Jiang S,Dupont N. Autophagy intersections with conventional and unconventional secretion in tissue development,remodeling and inflammation. Trends Cell Biol,2012,22(8):397-406.
[32]Florey O,Kim S E,Sandoval C P,et al. Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranes. Nat Cell Biol,2011,13(11):1335-1343.
[33] Martinez J, Almendinger J, Oberst A, et al Microtubuleassociated protein 1 light chain 3 alpha(LC3)-associated phagocytosis is required for the efficient clearance of dead cells.Proc Natl Acad Sci USA,2011,108(42):17396-17401.
[34]Fletcher K,Ulferts R,Jacquin E,et al. The WD40 domain of ATG16L1 is required for its non-canonical role in lipidation of LC3 at single membranes. EMBO J,2018,37(4):e97840.
[35]Codogno P,Mehrpour M,Proikas-Cezanne T. Canonical and noncanonical autophagy:variations on a common theme of selfeating. Nat Rev Mol Cell Biol,2011,13(1):7-12.
[36]Jacquin E,Leclerc-Mercier S,Judon C,et al. Pharmacological modulators of autophagy activate a parallel noncanonical pathway driving unconventional LC3 lipidation. Autophagy,2017,13(5):854-867.
[37] Tooze S A,Abada A,Elazar Z. Endocytosis and autophagy:exploitation or cooperation. Cold Spring Harbor Perspect Biol,2014,6(5):a018358.
[38]Guo H,Chitiprolu M,Roncevic L,et al. Atg5 disassociates the V1V0-ATPase to promote exosome production and tumor metastasis independent of canonical macroautophagy. Dev Cell,2017,43(6):716-730.
[39]Murrow L,Malhotra R,Debnath J. ATG12-ATG3 interacts with Alix to promote basal autophagic flux and late endosome function.Nat Cell Biol,2015,17(3):300-310.
[40] Martinez J, Malireddi R K, Lu Q, et al. Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon,NOX2 and autophagy proteins. Nat Cell Biol,2015,17(7):893-906.
[41] Liu J,Zhang Y,Liu A,et al. Distinct dasatinib-induced mechanisms of apoptotic response and exosome release in imatinibresistant human chronic myeloid leukemia cells. Int J Mol Sci,2016,17(4):531.
[42] Bader CA,Shandala T,Ng Y S,et al. Atg9 is required for intraluminal vesicles in amphisomes and autolysosomes. Biol Open,2015,4(11):1345-1355.
[43]Liou W,Geuze H J,Geelen M J,et al. The autophagic and endocytic pathways converge at the nascent autophagic vacuoles. J Cell Biol,1997,136(1):61-70.
[44]Fade C M,Snchez D,Furln M,et al. Induction of autophagy promotes fusion of multivesicular bodies with autophagic vacuoles in k562 cells. Traffic,2008,9(2):230-250.
[45]Villarroya-Beltri C,Baixauli F,Mittelbrunn M,et al. ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins. Nat Commun,2016,7:13588.
[46] Hurwitz S N,Cheerathodi M R,Nkosi D,et al. Tetraspanin CD63 bridges autophagic and endosomal processes to regulate exosomal secretion and intracellular signaling of Epstein-Barr virus LMP1. J Virol,2018,92(5):e01969-17.
[47] Patel K K,Miyoshi H,Beatty W L,et al. Autophagy proteins control goblet cell function by potentiating reactive oxygen species production. EMBO J,2013,32(4):3130-3144.
[48]Chen Y D,Fang Y T,Cheng Y L,et al. Exophagy of annexin A2via RAB11, RAB8A and RAB27A in IFN-γ-stimulated lung epithelial cells. Sci Rep,2017,7(1):5676.
[49]Bukong T N,Momen-Heravi F,Kodys K,et al. Exosomes from hepatitis C infected patients transmit HCV infection and contain replication competent viral RNA in complex with Ago2-miR122-HSP90. PLo S Pathog,2014,10(10):e1004424.
[50] Liu Z,Zhang X,Yu Q,et al. Exosome-associated hepatitis C virus in cell cultures and patient plasma. Biochem Biophys Res Commun,2014,455(3-4):218-222.
[51]Shrivastava S,Devhare P,Sujijantarat N,et al. Knockdown of autophagy inhibits infectious hepatitis C virus release by the exosomal pathway. J Virol,2015,90(3):1387-1396.
[52] Ren H,Elgner F,Jiang B,et al. The autophagosomal SNARE protein syntaxin 17 is an essential factor for the hepatitis C virus life cycle. J Virol,2016,90(13):5989-6000.
[53]Wang L,Tian Y,Ou J J,et al. HCV induces the expression of Rubicon and UVRAG to temporally regulate the maturation of autophagosomes and viral replication. PLo S Pathog,2015,11(3):e1004764.