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首页> 外文期刊>Biochimica et biophysica acta. Molecular cell research >TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways.
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TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways.

机译:TI-VAMP / VAMP7和VAMP3 / cellubrevin:两种v-SNARE蛋白,参与自噬/多囊泡体途径的特定步骤。

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摘要

During reticulocyte maturation, some membrane proteins and organelles that are not required in the mature red cell are lost. Several of these proteins are released into the extracellular medium associated with the internal vesicles present in multivesicular bodies (MVBs). Likewise, organelles such as mitochondria and endoplasmic reticulum are wrapped into double membrane vacuoles (i.e., autophagosomes) and degraded via autophagy. Morphological, molecular, and biochemical studies have shown that autophagosomes fuse with MVBs forming the so-called amphisomes, a prelysosomal hybrid organelle. SNAREs are key molecules of the vesicle fusion machinery. TI-VAMP/VAMP7 and VAMP3/cellubrevin are two v-SNARE proteins involved in the endocytic and exocytic pathways. We have previously shown that in the human leukemic K562 cells, Rab11 decorates MVBs and it is necessary for fusion between autophagosomes with MVBs. In the present report, we present evidence indicating that VAMP3 is required for the fusion between MVBs with autophagosomes to generate the amphisome, allowing the maturation of the autophagosome, but it does not seem to be involved in the next step, i. e., fusion with the lysosome. On the other hand, we demonstrate that VAMP7 is necessary for this latter event, allowing the completion of the autophagic pathway. Furthermore, VAMP7 and ATPase NSF, a protein required for SNAREs disassembly, participate in the fusion between MVBs with the plasma membrane to release the internal vesicles (i.e., exosomes) into the extracellular medium.
机译:在网状细胞成熟期间,成熟红细胞不需要的一些膜蛋白和细胞器会丢失。这些蛋白质中的几种被释放到与存在于多囊泡体(MVB)中的内部囊泡相关的细胞外介质中。同样地,诸如线粒体和内质网的细胞器被包裹在双膜液泡(即自噬体)中并通过自噬降解。形态,分子和生化研究表明,自噬体与MVB融合形成了所谓的两性体,即溶酶体杂合细胞器。 SNARE是囊泡融合机器的关键分子。 TI-VAMP / VAMP7和VAMP3 / cellubrevin是参与内吞和外吞途径的两个v-SNARE蛋白。先前我们已经表明,在人类白血病K562细胞中,Rab11修饰MVB,自噬体与MVB融合是必需的。在本报告中,我们提供了证据表明MVB与自噬小体融合以生成两亲体需要VAMP3,从而使自噬小体成熟,但似乎不参与下一步,即。例如,与溶酶体融合。另一方面,我们证明了VAMP7对于后者事件是必需的,从而使自噬途径得以完成。此外,VAMP7和ATPase NSF(SNARE分解所需的蛋白质)参与MVB与质膜的融合,从而将内部囊泡(即外泌体)释放到细胞外介质中。

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