Morelli Elena, Speranza Elisa A, Pellegrino Enrica, Beznoussenko Galina V, Carminati Francesca, Garré Massimiliano, Mironov Alexander A, Onorati Marco, Vaccari Thomas
Dipartimento di Bioscienze, Università degli Studi di Milano, Milan, Italy.
Dipartimento di Biologia, Unità di Biologia Cellulare e dello Sviluppo, Università di Pisa, Pisa, Italy.
Front Cell Dev Biol. 2021 Feb 18;9:637565. doi: 10.3389/fcell.2021.637565. eCollection 2021.
Snap29 is a conserved regulator of membrane fusion essential to complete autophagy and to support other cellular processes, including cell division. In humans, inactivating mutations causes CEDNIK syndrome, a rare multi-systemic disorder characterized by congenital neuro-cutaneous alterations. The fibroblasts of CEDNIK patients show alterations of the Golgi apparatus (GA). However, whether and how Snap29 acts at the GA is unclear. Here we investigate SNAP29 function at the GA and endoplasmic reticulum (ER). As part of the elongated structures in proximity to these membrane compartments, a pool of SNAP29 forms a complex with Syntaxin18, or with Syntaxin5, which we find is required to engage SEC22B-loaded vesicles. Consistent with this, in HeLa cells, in neuroepithelial stem cells, and , decreased SNAP29 activity alters GA architecture and reduces ER to GA trafficking. Our data reveal a new regulatory function of Snap29 in promoting secretory trafficking.
Snap29是膜融合的保守调节因子，对完成自噬和支持包括细胞分裂在内的其他细胞过程至关重要。在人类中，失活突变会导致CEDNIK综合征，这是一种罕见的多系统疾病，其特征为先天性神经皮肤改变。CEDNIK患者的成纤维细胞显示高尔基体（GA）发生改变。然而，Snap29是否以及如何在高尔基体发挥作用尚不清楚。在这里，我们研究了SNAP29在高尔基体和内质网（ER）中的功能。作为靠近这些膜隔室的细长结构的一部分，一部分SNAP29与Syntaxin18或Syntaxin5形成复合物，我们发现这是结合装载SEC22B的囊泡所必需的。与此一致的是，在HeLa细胞、神经上皮干细胞中，SNAP29活性降低会改变高尔基体结构并减少内质网到高尔基体的运输。我们的数据揭示了Snap29在促进分泌运输方面的新调节功能。
