Vats Somya, Galli Thierry
Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM U1266, Membrane Traffic in Healthy and Diseased Brain, Université Paris Cité, Paris, France.
GHU PARIS Psychiatrie & Neurosciences, Paris, France.
Front Cell Dev Biol. 2022 Jun 16;10:884020. doi: 10.3389/fcell.2022.884020. eCollection 2022.
Intracellular membrane protein trafficking is crucial for both normal cellular physiology and cell-cell communication. The conventional secretory route follows transport from the Endoplasmic reticulum (ER) to the plasma membrane via the Golgi apparatus. Alternative modes of secretion which can bypass the need for passage through the Golgi apparatus have been collectively termed as Unconventional protein secretion (UPS). UPS can comprise of cargo without a signal peptide or proteins which escape the Golgi in spite of entering the ER. UPS has been classified further depending on the mode of transport. Type I and Type II unconventional secretion are non-vesicular and non-SNARE protein dependent whereas Type III and Type IV dependent on vesicles and on SNARE proteins. In this review, we focus on the Type III UPS which involves the import of cytoplasmic proteins in membrane carriers of autophagosomal/endosomal origin and release in the extracellular space following SNARE-dependent intracellular membrane fusion. We discuss the role of vesicular SNAREs with a strong focus on VAMP7, a vesicular SNARE involved in exosome, lysosome and autophagy mediated secretion. We further extend our discussion to the role of unconventional secretion in health and disease with emphasis on cancer and neurodegeneration.
细胞内膜蛋白运输对于正常细胞生理和细胞间通讯都至关重要。传统的分泌途径是从内质网（ER）经高尔基体运输到质膜。能够绕过通过高尔基体这一需求的替代性分泌模式被统称为非常规蛋白分泌（UPS）。UPS可以包括没有信号肽的货物或尽管进入了内质网但仍能逃离高尔基体的蛋白质。UPS根据运输方式进一步分类。I型和II型非常规分泌是非囊泡且非SNARE蛋白依赖性的，而III型和IV型则依赖于囊泡和SNARE蛋白。在本综述中，我们聚焦于III型UPS，其涉及细胞质蛋白在自噬体/内体起源的膜载体中的导入，并在SNARE依赖性细胞内膜融合后释放到细胞外空间。我们讨论囊泡SNARE的作用，特别关注VAMP7，一种参与外泌体、溶酶体和自噬介导分泌的囊泡SNARE。我们进一步将讨论扩展到非常规分泌在健康和疾病中的作用，重点是癌症和神经退行性变。
