Four distinct cytoplasmic structures generate and release specific vesicles, thus opening the way to intercellular communication

G. Racchetti, J. Meldolesi
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Abstract

In all cells, generation and release of specific vesicles are the initial steps of back-and-forth intercellular communication. These processes are critical in normal physiology and pathophysiology. Vesicles have particular functions appropriate to their targets. When stimulated, they are released into the extracellular space. Four cytoplasmic membrane-bound structures generate their particular vesicles. Among these structures, multivesicular bodies (MVBs) can accumulate many small vesicles in their lumen; release occurs upon MVB exocytosis. Ectosomes are larger vesicles characterized by their responses and are generated directly and released independently from specific microdomains pre-established in the thickness of the plasma membrane. Most lysosomes do not generate vesicles. However, unique components of a minor form, the endo-lysosome, constitute the third class of structures that release a few vesicles by exocytosis with molecules and structures inducing changes in the extracellular environment. The autophagosome, the fourth structure, releases several heterogeneous vesicles by exocytosis with malformed bio-molecules, assembled structures, and damaged organelles. Interestingly, the frequent interaction of autophagosomes with MVBs and their exosomes contributes to the regulation and intensity of their action. The specificity and function of released vesicles depend on their membranes’ and luminal cargoes’ composition and dynamics. An ongoing investigation of the various vesicles reveals new properties regarding their generation, release, and resulting extracellular processes. The growth of information about structures and their vesicles progressively extends the knowledge base regarding cell communication and contributes to their clinical applications.
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四种不同的细胞质结构产生和释放特定的囊泡,从而开辟了细胞间通讯的途径
在所有细胞中,特定囊泡的产生和释放是细胞间来回通讯的初始步骤。这些过程在正常生理和病理生理中至关重要。囊泡具有与其靶物相适应的特殊功能。当受到刺激时,它们被释放到细胞外空间。四种细胞质膜结合结构产生它们特有的囊泡。在这些结构中,多泡体(MVBs)可以在其腔内积聚许多小泡;释放发生在MVB胞吐。外泌体是一种更大的囊泡,其特征在于它们的反应,并且直接产生并独立于预先建立在质膜厚度上的特定微域释放。大多数溶酶体不产生囊泡。然而,一种次要形式的独特成分,即内溶酶体,构成了第三类结构,通过胞吐作用释放一些囊泡,其分子和结构诱导细胞外环境的变化。第四种结构是自噬体,它通过胞吐作用释放出带有畸形生物分子、组装结构和受损细胞器的异质囊泡。有趣的是,自噬体与MVBs及其外泌体的频繁相互作用有助于其作用的调节和强度。释放囊泡的特异性和功能取决于其膜和腔内货物的组成和动力学。对各种囊泡的持续研究揭示了它们的产生、释放和由此产生的细胞外过程的新特性。关于结构及其囊泡的信息的增长逐渐扩展了关于细胞通讯的知识库,并有助于它们的临床应用。
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