SNX5 targets a monoamine transporter to the TGN for assembly into dense core vesicles by AP-3.
SNX5 targets a monoamine transporter to the TGN for assembly into dense core vesicles by AP-3.
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DOI：
10.1083/jcb.202106083
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发表时间：
2022-05-02
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--
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内体接头蛋白AP-3组装致密核心小泡(DCV)的膜蛋白。分选Nexin 5通过将囊泡单胺转运蛋白(VMAT)从内体逆行转运到跨高尔基体网络(TGN)来靶向DCV，从而揭示了AP-3在TGN中的新作用。多肽激素、神经肽和其他神经调节剂传递信号的时间进程取决于它们在致密核心小泡(DCV)中的存储。接合蛋白3(AP-3)是一种膜蛋白，可以调节DCV的释放，并能促进DCV从内体直接转运到成熟的DCV。我们现在发现，DCV中受调控的单胺释放需要排序Nexin 5(SNX5)。SNX5的缺失扰乱了囊泡单胺转运体(VMAT)向DCV的运输。该机制涉及SNX5在VMAT从内体到TGN的逆行运输中的作用。然而，SNX5的这种作用与AP-3从内体直接运输到DCV的拟议功能相冲突。我们现在确定AP-3在TGN的临时角色，在那里它与DCV货物相关联。因此，SNX5从内体逆行转运使AP-3能够在TGN组装DCV，从而解决了明显的拮抗作用。AP-3在TGN中的一个新作用对其他也依赖于该适配器的细胞器也有意义。
The endosomal adaptor protein AP-3 assembles the membrane proteins of dense core vesicles (DCVs). Sorting nexin 5 targets the vesicular monoamine transporter (VMAT) to DCVs by retrograde transport from endosomes to the trans-Golgi network (TGN), thereby revealing a novel role for AP-3 at the TGN. The time course of signaling by peptide hormones, neural peptides, and other neuromodulators depends on their storage inside dense core vesicles (DCVs). Adaptor protein 3 (AP-3) assembles the membrane proteins that confer regulated release of DCVs and is thought to promote their trafficking from endosomes directly to maturing DCVs. We now find that regulated monoamine release from DCVs requires sorting nexin 5 (SNX5). Loss of SNX5 disrupts trafficking of the vesicular monoamine transporter (VMAT) to DCVs. The mechanism involves a role for SNX5 in retrograde transport of VMAT from endosomes to the TGN. However, this role for SNX5 conflicts with the proposed function of AP-3 in trafficking from endosomes directly to DCVs. We now identify a transient role for AP-3 at the TGN, where it associates with DCV cargo. Thus, retrograde transport from endosomes by SNX5 enables DCV assembly at the TGN by AP-3, resolving the apparent antagonism. A novel role for AP-3 at the TGN has implications for other organelles that also depend on this adaptor.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
25
作者：
Goh GY;Huang H;Ullman J;Borre L;Hnasko TS;Trussell LO;Edwards RH
通讯作者：
Edwards RH
影响因子：
3.3
作者：
Kaur H;Sparvoli D;Osakada H;Iwamoto M;Haraguchi T;Turkewitz AP
通讯作者：
Turkewitz AP
DOI：
10.1007/5584_2018_185
发表时间：
2019-01-01
期刊：
PROTEIN REVIEWS - PURINERGIC RECEPTORS, VOL 20
影响因子：
--
作者：
Chandra, Mintu;Collins, Brett M.
通讯作者：
Collins, Brett M.
影响因子：
16.2
作者：
Ailion M;Hannemann M;Dalton S;Pappas A;Watanabe S;Hegermann J;Liu Q;Han HF;Gu M;Goulding MQ;Sasidharan N;Schuske K;Hullett P;Eimer S;Jorgensen EM
通讯作者：
Jorgensen EM