【《III型非经典分泌概述》4400字】

III型非经典分泌概述目录TOC\o"1-3"\h\u17337III型非经典分泌概述 1302261.1分泌型溶酶体 140781.2微囊泡介导的分泌 2324031.3外泌体介导的分泌 2207721.4错误折叠蛋白相关分泌 3175071.5分泌型自噬 3III型非经典分泌途径又被称为囊泡介导的非经典分泌，该过程中无引导蛋白需要被包装进膜泡载体中，包括自噬体（autophagosome），溶酶体（lysosome）和内体（endosome）等。到目前为止，已经有大量的关于III型UPS机制的研究ADDINEN.CITEADDINEN.CITE.DATA(Dupontetal.,2011;Ejlerskovetal.,2013;LotzeandTracey,2005)。1.1分泌型溶酶体AnnaRubartelli实验室1990年发现在激活状态的单核细胞中，IL-1β存在于胞内的某些膜泡结构中，这些膜泡可能介导IL-1β的分泌ADDINEN.CITE<EndNote><Cite><Author>Rubartelli</Author><Year>1990</Year><RecNum>71</RecNum><DisplayText>(Rubartellietal.,1990)</DisplayText><record><rec-number>71</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612446339">71</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Rubartelli,Anna</author><author>Cozzolino,F</author><author>Talio,M</author><author>Sitia,R</author></authors></contributors><titles><title>Anovelsecretorypathwayforinterleukin‐1beta,aproteinlackingasignalsequence</title><secondary-title>TheEMBOjournal</secondary-title></titles><periodical><full-title>TheEMBOjournal</full-title></periodical><pages>1503-1510</pages><volume>9</volume><number>5</number><dates><year>1990</year></dates><isbn>0261-4189</isbn><urls></urls></record></Cite></EndNote>(Rubartellietal.,1990)。后续的研究发现，pro-IL-1β存在于与内体和早期溶酶体共组分的膜泡中，抑制内吞溶酶体蛋白酶活性并促进IL-1β的分泌，而升高腔内pH则抑制膜泡的积累和IL-1β的分泌，同时低渗条件和胞外ATP可以调节含有pro-IL-1β膜泡的胞吐。据此，他们提出了一个膜泡介导IL-1β分泌的两步模型：胞质pro-IL-1β首先通过跨膜转位进入到内吞溶酶体相关的膜泡中，然后通过与细胞质膜融合将IL-1β释放到胞外ADDINEN.CITE<EndNote><Cite><Author>Andrei</Author><Year>1999</Year><RecNum>72</RecNum><DisplayText>(Andreietal.,1999)</DisplayText><record><rec-number>72</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612446683">72</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Andrei,Cristina</author><author>Dazzi,Cecilia</author><author>Lotti,Lavinia</author><author>Torrisi,MariaRosaria</author><author>Chimini,Giovanna</author><author>Rubartelli,Anna</author></authors></contributors><titles><title>Thesecretoryrouteoftheleaderlessproteininterleukin1βinvolvesexocytosisofendolysosome-relatedvesicles</title><secondary-title>Molecularbiologyofthecell</secondary-title></titles><periodical><full-title>Molecularbiologyofthecell</full-title></periodical><pages>1463-1475</pages><volume>10</volume><number>5</number><dates><year>1999</year></dates><isbn>1059-1524</isbn><urls></urls></record></Cite></EndNote>(Andreietal.,1999)（图1.4）。之后他们又证明在树突状细胞中存在Ca2+依赖的分泌型溶酶体胞外分泌途径ADDINEN.CITE<EndNote><Cite><Author>Gardella</Author><Year>2001</Year><RecNum>74</RecNum><DisplayText>(Gardellaetal.,2001)</DisplayText><record><rec-number>74</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612515966">74</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Gardella,Stefania</author><author>Andrei,Cristina</author><author>Lotti,LaviniaVittoria</author><author>Poggi,Alessandro</author><author>Torrisi,MRosaria</author><author>Zocchi,MRaffaella</author><author>Rubartelli,Anna</author></authors></contributors><titles><title>CD8+Tlymphocytesinducepolarizedexocytosisofsecretorylysosomesbydendriticcellswithreleaseofinterleukin-1βandcathepsinD</title><secondary-title>Blood,TheJournaloftheAmericanSocietyofHematology</secondary-title></titles><periodical><full-title>Blood,TheJournaloftheAmericanSocietyofHematology</full-title></periodical><pages>2152-2159</pages><volume>98</volume><number>7</number><dates><year>2001</year></dates><isbn>1528-0020</isbn><urls></urls></record></Cite></EndNote>(Gardellaetal.,2001)。此外，高迁移率家族蛋白1（highmobilitygroupprotein,HMGB1）在溶血卵磷脂（lysophosphatidylcholine,LPC）刺激的单核细胞中通过分泌型溶酶体途径释放ADDINEN.CITE<EndNote><Cite><Author>Gardella</Author><Year>2002</Year><RecNum>75</RecNum><DisplayText>(Gardellaetal.,2002)</DisplayText><record><rec-number>75</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612516268">75</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Gardella,Stefania</author><author>Andrei,Cristina</author><author>Ferrera,Denise</author><author>Lotti,LaviniaV</author><author>Torrisi,MariaR</author><author>Bianchi,MarcoE</author><author>Rubartelli,Anna</author></authors></contributors><titles><title>ThenuclearproteinHMGB1issecretedbymonocytesviaanon‐classical,vesicle‐mediatedsecretorypathway</title><secondary-title>EMBOreports</secondary-title></titles><periodical><full-title>EMBOreports</full-title></periodical><pages>995-1001</pages><volume>3</volume><number>10</number><dates><year>2002</year></dates><isbn>1469-3178</isbn><urls></urls></record></Cite></EndNote>(Gardellaetal.,2002)，脂肪细胞的胞质脂肪酸结合蛋白4（cytoplasmicfattyacidbindingprotein4,FABP4）可以通过分泌型溶酶体分泌到胞外发挥功能ADDINEN.CITE<EndNote><Cite><Author>Villeneuve</Author><Year>2018</Year><RecNum>29</RecNum><DisplayText>(Villeneuveetal.,2018)</DisplayText><record><rec-number>29</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612106637">29</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Villeneuve,Julien</author><author>Bassaganyas,Laia</author><author>Lepreux,Sebastien</author><author>Chiritoiu,Marioara</author><author>Costet,Pierre</author><author>Ripoche,Jean</author><author>Malhotra,Vivek</author><author>Schekman,Randy</author></authors></contributors><titles><title>UnconventionalsecretionofFABP4byendosomesandsecretorylysosomes</title><secondary-title>JournalofCellBiology</secondary-title></titles><periodical><full-title>JournalofCellBiology</full-title></periodical><pages>649-665</pages><volume>217</volume><number>2</number><dates><year>2018</year></dates><isbn>0021-9525</isbn><urls></urls></record></Cite></EndNote>(Villeneuveetal.,2018)。图1.4IL-1β通过分泌型溶酶体分泌模型ADDINEN.CITE<EndNote><Cite><Author>Andrei</Author><Year>1999</Year><RecNum>72</RecNum><DisplayText>(Andreietal.,1999)</DisplayText><record><rec-number>72</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612446683">72</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Andrei,Cristina</author><author>Dazzi,Cecilia</author><author>Lotti,Lavinia</author><author>Torrisi,MariaRosaria</author><author>Chimini,Giovanna</author><author>Rubartelli,Anna</author></authors></contributors><titles><title>Thesecretoryrouteoftheleaderlessproteininterleukin1βinvolvesexocytosisofendolysosome-relatedvesicles</title><secondary-title>Molecularbiologyofthecell</secondary-title></titles><periodical><full-title>Molecularbiologyofthecell</full-title></periodical><pages>1463-1475</pages><volume>10</volume><number>5</number><dates><year>1999</year></dates><isbn>1059-1524</isbn><urls></urls></record></Cite></EndNote>(Andreietal.,1999)胞质pro-IL-1β首先通过跨膜转位进入到内吞溶酶体相关的膜泡中，然后通过与细胞质膜融合将IL-1β释放到胞外。1.2微囊泡介导的分泌有文献报道，无引导蛋白也可以通过微囊泡（microvesicles）的方式被分泌到胞外。2001年，AnnmarieSurprenant实验室发现被外源ATP激活P2X7受体2-3s的THP-1单核细胞会从质膜上脱落形成微囊泡。2min后，可以在这些微囊泡中检测到具有生物活性的IL-1β，随后IL-1β会出现在没有小泡的上清中ADDINEN.CITE<EndNote><Cite><Author>MacKenzie</Author><Year>2001</Year><RecNum>145</RecNum><DisplayText>(MacKenzieetal.,2001)</DisplayText><record><rec-number>145</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612922149">145</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>MacKenzie,Amanda</author><author>Wilson,HeatherL</author><author>Kiss-Toth,Endre</author><author>Dower,StevenK</author><author>North,RAlan</author><author>Surprenant,Annmarie</author></authors></contributors><titles><title>Rapidsecretionofinterleukin-1βbymicrovesicleshedding</title><secondary-title>Immunity</secondary-title></titles><periodical><full-title>Immunity</full-title></periodical><pages>825-835</pages><volume>15</volume><number>5</number><dates><year>2001</year></dates><isbn>1074-7613</isbn><urls></urls></record></Cite></EndNote>(MacKenzieetal.,2001)。之后，在小胶质细胞（microglia）中也发现ATP诱导的微泡脱落可以介导IL-1β的释放ADDINEN.CITE<EndNote><Cite><Author>Bianco</Author><Year>2005</Year><RecNum>146</RecNum><DisplayText>(Biancoetal.,2005)</DisplayText><record><rec-number>146</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612923086">146</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Bianco,Fabio</author><author>Pravettoni,Elena</author><author>Colombo,Alessio</author><author>Schenk,Ursula</author><author>Möller,Thomas</author><author>Matteoli,Michela</author><author>Verderio,Claudia</author></authors></contributors><titles><title>Astrocyte-derivedATPinducesvesiclesheddingandIL-1βreleasefrommicroglia</title><secondary-title>TheJournalofImmunology</secondary-title></titles><periodical><full-title>TheJournalofImmunology</full-title></periodical><pages>7268-7277</pages><volume>174</volume><number>11</number><dates><year>2005</year></dates><isbn>0022-1767</isbn><urls></urls></record></Cite></EndNote>(Biancoetal.,2005)。在这个系统中，星形胶质细胞（astrocytes）释放的ATP不仅在触发小胶质细胞微泡脱落中发挥了重要作用，而且在微囊泡膜上诱导了依赖P2X7受体的孔道的形成，使细胞因子被释放。1.3外泌体介导的分泌2007年，GeorgeR.Dubyak实验室提出IL-1β也可以通过外泌体（exosomes）被释放ADDINEN.CITE<EndNote><Cite><Author>Qu</Author><Year>2007</Year><RecNum>147</RecNum><DisplayText>(Quetal.,2007)</DisplayText><record><rec-number>147</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612923622">147</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Qu,Yan</author><author>Franchi,Luigi</author><author>Nunez,Gabriel</author><author>Dubyak,GeorgeR</author></authors></contributors><titles><title>NonclassicalIL-1βsecretionstimulatedbyP2X7receptorsisdependentoninflammasomeactivationandcorrelatedwithexosomereleaseinmurinemacrophages</title><secondary-title>TheJournalofImmunology</secondary-title></titles><periodical><full-title>TheJournalofImmunology</full-title></periodical><pages>1913-1925</pages><volume>179</volume><number>3</number><dates><year>2007</year></dates><isbn>0022-1767</isbn><urls></urls></record></Cite></EndNote>(Quetal.,2007)。在他们的研究中，P2X7受体激活并诱导多泡小体（multivesiclesbody,MVB）的形成，这些MVB可以和细胞质膜直接融合释放含有IL-1β，Caspase-1和其它炎性小体成分的外泌体。有趣的是，炎性小体的组装以及活化的Caspase-1会引起IL-1β的分泌，这也支持之前的实验结果，即IL-1β的加工和分泌是相关的ADDINEN.CITE<EndNote><Cite><Author>Andrei</Author><Year>1999</Year><RecNum>72</RecNum><DisplayText>(Andreietal.,1999;Andreietal.,2004)</DisplayText><record><rec-number>72</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612446683">72</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Andrei,Cristina</author><author>Dazzi,Cecilia</author><author>Lotti,Lavinia</author><author>Torrisi,MariaRosaria</author><author>Chimini,Giovanna</author><author>Rubartelli,Anna</author></authors></contributors><titles><title>Thesecretoryrouteoftheleaderlessproteininterleukin1βinvolvesexocytosisofendolysosome-relatedvesicles</title><secondary-title>Molecularbiologyofthecell</secondary-title></titles><periodical><full-title>Molecularbiologyofthecell</full-title></periodical><pages>1463-1475</pages><volume>10</volume><number>5</number><dates><year>1999</year></dates><isbn>1059-1524</isbn><urls></urls></record></Cite><Cite><Author>Andrei</Author><Year>2004</Year><RecNum>148</RecNum><record><rec-number>148</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612924307">148</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Andrei,Cristina</author><author>Margiocco,Paola</author><author>Poggi,Alessandro</author><author>Lotti,LaviniaV</author><author>Torrisi,MR</author><author>Rubartelli,Anna</author></authors></contributors><titles><title>PhospholipasesCandA2controllysosome-mediatedIL-1βsecretion:implicationsforinflammatoryprocesses</title><secondary-title>ProceedingsoftheNationalAcademyofSciences</secondary-title></titles><periodical><full-title>ProceedingsoftheNationalAcademyofSciences</full-title></periodical><pages>9745-9750</pages><volume>101</volume><number>26</number><dates><year>2004</year></dates><isbn>0027-8424</isbn><urls></urls></record></Cite></EndNote>(Andreietal.,1999;Andreietal.,2004)。但是，目前仍不清楚外泌体中的IL-1β是如何从膜泡内游离出来并发挥功能的。1.4错误折叠蛋白相关分泌图1.5错误折叠蛋白相关分泌ADDINEN.CITE<EndNote><Cite><Author>Lee</Author><Year>2016</Year><RecNum>68</RecNum><DisplayText>(Leeetal.,2016a)</DisplayText><record><rec-number>68</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612416491">68</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Lee,Jin-Gu</author><author>Takahama,Shokichi</author><author>Zhang,Guofeng</author><author>Tomarev,StanislavI</author><author>Ye,Yihong</author></authors></contributors><titles><title>Unconventionalsecretionofmisfoldedproteinspromotesadaptationtoproteasomedysfunctioninmammaliancells</title><secondary-title>Naturecellbiology</secondary-title></titles><periodical><full-title>Naturecellbiology</full-title></periodical><pages>765-776</pages><volume>18</volume><number>7</number><dates><year>2016</year></dates><isbn>1476-4679</isbn><urls></urls></record></Cite></EndNote>(Leeetal.,2016a)胞质中错误折叠的蛋白被USP19招募到ER上，被包装进Rab9阳性的晚期内体中，之后晚期内体与细胞质膜发生融合，释放错误折叠蛋白到胞外。另一条新发现的分泌途径是错误折叠蛋白相关分泌（misfoldingassociatedproteinsecretion,MAPS）介导具有潜在细胞毒性多肽的释放，例如α-synuclein和Tau以及其他胞浆错误折叠的蛋白ADDINEN.CITE<EndNote><Cite><Author>Lee</Author><Year>2016</Year><RecNum>68</RecNum><DisplayText>(Leeetal.,2016a)</DisplayText><record><rec-number>68</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612416491">68</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Lee,Jin-Gu</author><author>Takahama,Shokichi</author><author>Zhang,Guofeng</author><author>Tomarev,StanislavI</author><author>Ye,Yihong</author></authors></contributors><titles><title>Unconventionalsecretionofmisfoldedproteinspromotesadaptationtoproteasomedysfunctioninmammaliancells</title><secondary-title>Naturecellbiology</secondary-title></titles><periodical><full-title>Naturecellbiology</full-title></periodical><pages>765-776</pages><volume>18</volume><number>7</number><dates><year>2016</year></dates><isbn>1476-4679</isbn><urls></urls></record></Cite></EndNote>(Leeetal.,2016a)。泛素特异性蛋白酶19（ubiquitin-specificprotease,USP19）是唯一具有跨膜结构域并定位于ER的去泛素酶，其催化结构域具有分子伴侣活性，可以将错误折叠的蛋白招募到ER表面进行去泛素化。去泛素化的蛋白通过DNAJC5被运送到Rab9阳性的晚期内体中。这些内体可能通过VAMP7/8依赖的方式与细胞质膜发生融合，将错误折叠的蛋白释放到胞外ADDINEN.CITE<EndNote><Cite><Author>Fontaine</Author><Year>2016</Year><RecNum>77</RecNum><DisplayText>(Fontaineetal.,2016)</DisplayText><record><rec-number>77</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612517649">77</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Fontaine,SarahN</author><author>Zheng,Dali</author><author>Sabbagh,JonathanJ</author><author>Martin,MackenzieD</author><author>Chaput,Dale</author><author>Darling,April</author><author>Trotter,JustinH</author><author>Stothert,AndrewR</author><author>Nordhues,BryceA</author><author>Lussier,April</author></authors></contributors><titles><title>DnaJ/Hsc70chaperonecomplexescontroltheextracellularreleaseofneurodegenerative‐associatedproteins</title><secondary-title>TheEMBOjournal</secondary-title></titles><periodical><full-title>TheEMBOjournal</full-title></periodical><pages>1537-1549</pages><volume>35</volume><number>14</number><dates><year>2016</year></dates><isbn>0261-4189</isbn><urls></urls></record></Cite></EndNote>(Fontaineetal.,2016)（图1.5）。错误折叠蛋白跨膜转位进入晚期内体是如何实现的尚不清楚，但考虑到晚期内体中存在LAMP2A，它可能依赖于分子伴侣介导的自噬（chaperonemediatedautophagy,CMA）途径。1.5分泌型自噬细胞自噬，长久以来都被认为是一种降解过程，在营养缺乏或应激状态下，细胞增加自噬降解胞质组分以起到促进生存的作用。然而，在过去的几十年里，越来越多的研究表明自噬与许多细胞组分的分泌密切相关ADDINEN.CITE<EndNote><Cite><Author>New</Author><Year>2019</Year><RecNum>79</RecNum><DisplayText>(NewandThomas,2019)</DisplayText><record><rec-number>79</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612620613">79</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>New,Jacob</author><author>Thomas,SufiMary</author></authors></contributors><titles><title>Autophagy-dependentsecretion:mechanism,factorssecreted,anddiseaseimplications</title><secondary-title>Autophagy</secondary-title></titles><periodical><full-title>Autophagy</full-title></periodical><pages>1682-1693</pages><volume>15</volume><number>10</number><dates><year>2019</year></dates><isbn>1554-8627</isbn><urls></urls></record></Cite></EndNote>(NewandThomas,2019)。自噬体不和溶酶体融合，而直接与细胞质膜融合，将胞质可溶蛋白，蛋白聚集体，细胞器和微生物释放到胞外ADDINEN.CITE<EndNote><Cite><Author>Claude-Taupin</Author><Year>2017</Year><RecNum>78</RecNum><DisplayText>(Claude-Taupinetal.,2017)</DisplayText><record><rec-number>78</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612620548">78</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Claude-Taupin,Aurore</author><author>Jia,Jingyue</author><author>Mudd,Michal</author><author>Deretic,Vojo</author></authors></contributors><titles><title>Autophagy’ssecretlife:secretioninsteadofdegradation</title><secondary-title>Essaysinbiochemistry</secondary-title></titles><periodical><full-title>Essaysinbiochemistry</full-title></periodical><pages>637-647</pages><volume>61</volume><number>6</number><dates><year>2017</year></dates><isbn>0071-1365</isbn><urls></urls></record></Cite></EndNote>(Claude-Taupinetal.,2017)（图1.6）。图1.6分泌型自噬促进多种胞质物质的释放ADDINEN.CITE<EndNote><Cite><Author>Claude-Taupin</Author><Year>2017</Year><RecNum>78</RecNum><DisplayText>(Claude-Taupinetal.,2017)</DisplayText><record><rec-number>78</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612620548">78</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Claude-Taupin,Aurore</author><author>Jia,Jingyue</author><author>Mudd,Michal</author><author>Deretic,Vojo</author></authors></contributors><titles><title>Autophagy’ssecretlife:secretioninsteadofdegradation</title><secondary-title>Essaysinbiochemistry</secondary-title></titles><periodical><full-title>Essaysinbiochemistry</full-title></periodical><pages>637-647</pages><volume>61</volume><number>6</number><dates><year>2017</year></dates><isbn>0071-1365</isbn><urls></urls></record></Cite></EndNote>(Claude-Taupinetal.,2017)自噬可以分为三类。代谢性自噬通过降解胞质蛋白来回收营养物质以维持代谢；质量控制自噬可以清除蛋白聚集体、受损或过多的细胞器以及入侵的微生物；分泌型自噬介导无引导蛋白的分泌。此外，分泌型自噬涉及到聚集性蛋白、微生物和细胞器（例如线粒体）的胞外释放。2010年首次发现乙酰辅酶A结合蛋白（AcetylCoAbindingproteins，酵母中为Acb1，盘基网柄菌中为AcbA，哺乳动物中为ACBP）的分泌与自噬有关ADDINEN.CITE<EndNote><Cite><Author>Duran</Author><Year>2010</Year><RecNum>66</RecNum><DisplayText>(Duranetal.,2010;Manjithayaetal.,2010)</DisplayText><record><rec-number>66</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612416380">66</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Duran,JuanM</author><author>Anjard,Christophe</author><author>Stefan,Chris</author><author>Loomis,WilliamF</author><author>Malhotra,Vivek</author></authors></contributors><titles><title>UnconventionalsecretionofAcb1ismediatedbyautophagosomes</title><secondary-title>Journalofcellbiology</secondary-title></titles><periodical><full-title>JournalofCellBiology</full-title></periodical><pages>527-536</pages><volume>188</volume><number>4</number><dates><year>2010</year></dates><isbn>1540-8140</isbn><urls></urls></record></Cite><Cite><Author>Manjithaya</Author><Year>2010</Year><RecNum>82</RecNum><record><rec-number>82</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612627815">82</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Manjithaya,Ravi</author><author>Anjard,Christophe</author><author>Loomis,WilliamF</author><author>Subramani,Suresh</author></authors></contributors><titles><title>UnconventionalsecretionofPichiapastorisAcb1isdependentonGRASPprotein,peroxisomalfunctions,andautophagosomeformation</title><secondary-title>JournalofCellBiology</secondary-title></titles><periodical><full-title>JournalofCellBiology</full-title></periodical><pages>537-546</pages><volume>188</volume><number>4</number><dates><year>2010</year></dates><isbn>1540-8140</isbn><urls></urls></record></Cite></EndNote>(Duranetal.,2010;Manjithayaetal.,2010)。在诱导自噬条件下，例如氮饥饿，Acb1的释放增加。在SEC基因突变和不表达ABC转运体Set6的MAT-α单倍体酵母中，细胞外的Acb1含量不发生变化，说明其分泌不是通过常规的ER-Golgi途径或ABC转运体途径。敲除自噬基因Atg5、Atg7、Atg8或Atg12后，Acb1分泌明显减少，但不影响胞内Acb1的浓度。Vam3/Vam7SNARE复合物和调节自噬小体与液泡融合的小GTPaseYpt7缺陷不影响Acb1的分泌，然而RabGTPaseYkt6（在内体循环中起作用）、液泡/内吞t-SNAREPep12、Tlg2和质膜t-SNARESso1是Acb1分泌所必需的。这些发现表明Acb1可能进入自噬体，然后和内体融合，这些含有Acb1的内体既可以成熟为MVB，也可以直接和质膜融合将Acb1释放到胞外（图1.7）。图1.7Acb1自噬依赖性分泌途径ADDINEN.CITE<EndNote><Cite><Author>Duran</Author><Year>2010</Year><RecNum>66</RecNum><DisplayText>(Duranetal.,2010)</DisplayText><record><rec-number>66</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612416380">66</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Duran,JuanM</author><author>Anjard,Christophe</author><author>Stefan,Chris</author><author>Loomis,WilliamF</author><author>Malhotra,Vivek</author></authors></contributors><titles><title>UnconventionalsecretionofAcb1ismediatedbyautophagosomes</title><secondary-title>Journalofcellbiology</secondary-title></titles><periodical><full-title>JournalofCellBiology</full-title></periodical><pages>527-536</pages><volume>188</volume><number>4</number><dates><year>2010</year></dates><isbn>1540-8140</isbn><urls></urls></record></Cite></EndNote>(Duranetal.,2010)胞质Acb1被包装进自噬体，与早期内体融合。含有Acb1的早期内体直接和质膜融合，或者成熟为MVB，MVB与细胞质膜融合释放Acb1。Grh1是Acb1分泌所必需的。Acb1的分泌严格依赖于Grh1（GRASP），在酿酒酵母饥饿时，Grh1聚集于靠近ERES的膜结构中。PI3P，ESCRT，Vps34和自噬相关蛋白Atg8，Atg9也会募集到这些Grh1膜泡结构，所以这一结构被命名为CUPS（compartmentforunconventionalproteinsecretion）ADDINEN.CITE<EndNote><Cite><Author>Bruns</Author><Year>2011</Year><RecNum>85</RecNum><DisplayText>(Brunsetal.,2011)</DisplayText><record><rec-number>85</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612699535">85</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Bruns,Caroline</author><author>McCaffery,JMichael</author><author>Curwin,AmyJ</author><author>Duran,JuanM</author><author>Malhotra,Vivek</author></authors></contributors><titles><title>Biogenesisofanovelcompartmentforautophagosome-mediatedunconventionalproteinsecretion</title><secondary-title>JournalofCellBiology</secondary-title></titles><periodical><full-title>JournalofCellBiology</full-title></periodical><pages>979-992</pages><volume>195</volume><number>6</number><dates><year>2011</year></dates><isbn>1540-8140</isbn><urls></urls></record></Cite></EndNote>(Brunsetal.,2011)。哺乳动物的GRASP蛋白，GRASP55和GRASP65都参与饥饿条件下IL-1β的分泌ADDINEN.CITE<EndNote><Cite><Author>Zhang</Author><Year>2015</Year><RecNum>86</RecNum><DisplayText>(Dupontetal.,2011;Zhangetal.,2015)</DisplayText><record><rec-number>86</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612699990">86</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Zhang,Min</author><author>Kenny,SamuelJ</author><author>Ge,Liang</author><author>Xu,Ke</author><author>Schekman,Randy</author></authors></contributors><titles><title>Translocationofinterleukin-1βintoavesicleintermediateinautophagy-mediatedsecretion</title><secondary-title>Elife</secondary-title></titles><periodical><full-title>Elife</full-title></periodical><pages>e11205</pages><volume>4</volume><dates><year>2015</year></dates><isbn>2050-084X</isbn><urls></urls></record></Cite><Cite><Author>Dupont</Author><Year>2011</Year><RecNum>69</RecNum><record><rec-number>69</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612445480">69</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Dupont,Nicolas</author><author>Jiang,Shanya</author><author>Pilli,Manohar</author><author>Ornatowski,Wojciech</author><author>Bhattacharya,Dhruva</author><author>Deretic,Vojo</author></authors></contributors><titles><title>Autophagy‐basedunconventionalsecretorypathwayforextracellulardeliveryofIL‐1β</title><secondary-title>TheEMBOjournal</secondary-title></titles><periodical><full-title>TheEMBOjournal</full-title></periodical><pages>4701-4711</pages><volume>30</volume><number>23</number><dates><year>2011</year></dates><isbn>0261-4189</isbn><urls></urls></record></Cite></EndNote>(Dupontetal.,2011;Zhangetal.,2015)，而GRASP55同时与自噬体的形成相关ADDINEN.CITE<EndNote><Cite><Author>Xie</Author><Year>2007</Year><RecNum>87</RecNum><DisplayText>(XieandKlionsky,2007)</DisplayText><record><rec-number>87</rec-number><foreign-keys><keyapp="EN"db-id="zeaxt9tw4v0aepewsv8vze20sd2s90at2s5a"timestamp="1612700147">87</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Xie,Zhiping</author><author>Klionsky,DanielJ</author></authors></contributors><titles><title>Autophagosomeformation:coremachineryandadaptations</title><secondary-title>Naturecellbiology</secondary-title></titles><periodical><full-title>Naturecellbiology</full-title></periodical><pages>1102-1109</pages><volume>9</volume><number>10</number><dates><year>2007</year></dates><isbn>1476-4679</isbn><urls></urls></record></Cite></EndNote>(XieandKlionsky,2007)。所以，CUPS一开始被认为可能是分泌型自噬体，然而Atg蛋白对酵母中CUPS的形成是非必需的ADDINEN.CITEADDINEN.CITE.DATA(Brunsetal.,2011;Cruz-Garciaetal.,2014;Curwinetal.,2016)。此外，除过Grh1，只有很少的蛋白因子同时参与Acb1的释放和CUPS的形成，表