Novel Therapeutic Strategies for Exosome-Related Diseases
Novel Therapeutic Strategies for Exosome-Related Diseases
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DOI：
10.33696/signaling.3.072
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发表时间：
2022-06
期刊：
影响因子：
--
通讯作者：
H. Ageta;K. Tsuchida
中科院分区：
文献类型：
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作者：
H. Ageta;K. Tsuchida
多泡体（MVB），也称为晚期内体，是富含腔内小泡（ILV）的特化内体区室的子集。多个ILV在MVB内累积[1，2]。ILV是通过早期内体的界膜内陷并出芽进入细胞器内腔而形成的。ILV隔离特定的蛋白质、脂质和胞质组分。虽然已知外泌体释放由MVB介导，但其调节尚未完全了解。一旦MVB与溶酶体融合，ILV的货物被降解。另一方面，当MVB与质膜融合时，ILV的内容物通过外泌体分泌到细胞外。大多数合成的蛋白质被翻译后修饰物修饰，其调节蛋白质的量、定位、稳定性和活性。翻译后修饰（PTM）参与细胞功能的调节[3]。已知MVB的形成受转运所需的内体分选复合物（ESCRT）系统[1]以及四跨膜蛋白和UBL的调节。ESCRT系统也依赖于泛素化[4]。近年来，泛素和UBLs被报道参与ILV和MVB的调控。将由泛素、SUMO或UBL 3修饰的蛋白质掺入MVB中。
The multivesicular body (MVB), also called late endosome, is a subset of specialized endosomal compartments rich in intraluminal vesicles (ILVs). Multiple ILVs accumulate within MVBs [1,2]. ILVs are formed by invagination of the limiting membrane of early endosomes and budding into the lumen of the organelle. ILVs sequester specific proteins, lipids and cytosolic components. Although exosome release is known to be mediated by MVB, its regulation is not fully understood. Once MVBs fuse with lysosomes, the cargo of the ILVs is degraded. On the other hand, when MVBs fuse with the plasma membrane, the contents of ILVs are secreted outside the cell via exosomes. Most synthesized proteins are modified by post-translational modifiers, which regulate the amount, localization, stability, and activity of proteins. Post-translational modifications (PTM) are involved in the regulation of cellular functions [3]. The formation of MVB is known to be regulated by the endosomal sorting complexes required for transport (ESCRT) systems [1], as well as tetraspanins and UBLs. ESCRT systems are also dependent on ubiquitination [4]. Recently, ubiquitin and UBLs were reported to be involved in the regulation of ILV and MVB. Proteins modified by ubiquitin, SUMO, or UBL3 were incorporated into MVB.