Organelle tethering, pore formation and SNARE compensation in the late endocytic pathway.
Organelle tethering, pore formation and SNARE compensation in the late endocytic pathway.
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DOI：
10.1242/jcs.255463
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发表时间：
2021-05-15
影响因子：
4
通讯作者：
Luzio JP
中科院分区：
文献类型：
--
作者：
Davis LJ;Bright NA;Edgar JR;Parkinson MDJ;Wartosch L;Mantell J;Peden AA;Luzio JP
为了深入了解导致内吞递送至溶酶体的吻跑和完全融合事件，我们研究了引起HeLa细胞中晚期内吞细胞器之间的束缚和孔形成增加的条件。敲除的可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）VAMP 7和VAMP 8显示，通过电子显微镜，拴系溶酶体相关膜蛋白（LAMP）载体囊泡周围的多泡体的积累，以及外观的“沙漏”的轮廓后期内吞细胞器连接丝状栓，但并没有阻止内吞传递到溶酶体水解酶。随后SNARE YKT 6的耗尽减少了这种递送，与其补偿VAMP 7和VAMP 8的缺失一致。我们还研究了多囊泡体和扩大的内溶酶体之间的丝状拴系后，耗尽带电的多囊泡体蛋白6（CHMP 6），并提供了第一个证据，孔形成开始在系绳阵列的边缘，与孔扩张所需的全膜融合。总结：通过吻和运行/膜融合的内吞递送到溶酶体需要在系链阵列的边缘开始的孔形成，并且证明了SNARE冗余和补偿。
To provide insights into the kiss-and-run and full fusion events resulting in endocytic delivery to lysosomes, we investigated conditions causing increased tethering and pore formation between late endocytic organelles in HeLa cells. Knockout of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) VAMP7 and VAMP8 showed, by electron microscopy, the accumulation of tethered lysosome-associated membrane protein (LAMP)-carrier vesicles around multivesicular bodies, as well as the appearance of ‘hourglass’ profiles of late endocytic organelles attached by filamentous tethers, but did not prevent endocytic delivery to lysosomal hydrolases. Subsequent depletion of the SNARE YKT6 reduced this delivery, consistent with it compensating for the absence of VAMP7 and VAMP8. We also investigated filamentous tethering between multivesicular bodies and enlarged endolysosomes following depletion of charged multi-vesicular body protein 6 (CHMP6), and provide the first evidence that pore formation commences at the edge of tether arrays, with pore expansion required for full membrane fusion. Summary: Endocytic delivery to lysosomes by kiss and run/membrane fusion entails pore formation commencing at the edge of tether arrays, and demonstrates SNARE redundancy and compensation.
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影响因子：
9.2
作者：
Bright, Nicholas A.;Davis, Luther J.;Luzio, J. Paul
通讯作者：
Luzio, J. Paul
影响因子：
64.8
作者：
Bao H;Das D;Courtney NA;Jiang Y;Briguglio JS;Lou X;Roston D;Cui Q;Chanda B;Chapman ER
通讯作者：
Chapman ER
DOI：
10.1073/pnas.1307074110
发表时间：
2013-08-13
影响因子：
11.1
作者：
Graham, Stephen C.;Wartosch, Lena;Owen, David J.
通讯作者：
Owen, David J.
DOI：
10.1083/jcb.201804028
发表时间：
2018-10-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bas L;Papinski D;Licheva M;Torggler R;Rohringer S;Schuschnig M;Kraft C
通讯作者：
Kraft C
影响因子：
9.8
作者：
Jaiswal JK;Chakrabarti S;Andrews NW;Simon SM
通讯作者：
Simon SM