Department of Biology, Concordia University, Montreal, Quebec, Canada.
Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada.
Traffic. 2019 Jan;20(1):5-26. doi: 10.1111/tra.12615. Epub 2018 Sep 24.
The movement of proteins between cellular compartments requires the orchestrated actions of many factors including Rab family GTPases, Soluble NSF Attachment protein REceptors (SNAREs) and so-called tethering factors. One such tethering factor is called TRAnsport Protein Particle (TRAPP), and in humans, TRAPP proteins are distributed into two related complexes called TRAPP II and III. Although thought to act as a single unit within the complex, in the past few years it has become evident that some TRAPP proteins function independently of the complex. Consistent with this, variations in the genes encoding these proteins result in a spectrum of human diseases with diverse, but partially overlapping, phenotypes. This contrasts with other tethering factors such as COG, where variations in the genes that encode its subunits all result in an identical phenotype. In this review, we present an up-to-date summary of all the known disease-related variations of genes encoding TRAPP-associated proteins and the disorders linked to these variations which we now call TRAPPopathies.
蛋白质在细胞区室之间的运动需要许多因素的协调作用，包括 Rab 家族 GTPases、可溶性 NSF 附着蛋白受体 (SNAREs) 和所谓的 tethering 因子。这样的 tethering 因子之一称为运输蛋白颗粒 (TRAPP)，在人类中，TRAPP 蛋白分为两个相关的复合物，称为 TRAPP II 和 III。尽管被认为在复合物中作为一个单一的单元起作用，但在过去的几年中，已经明显表明一些 TRAPP 蛋白独立于复合物起作用。与此一致的是，编码这些蛋白质的基因的变异导致一系列具有不同但部分重叠表型的人类疾病。这与其他 tethering 因子（如 COG）形成对比，其中编码其亚基的基因的变异都导致相同的表型。在这篇综述中，我们总结了所有已知与 TRAPP 相关蛋白编码基因的疾病相关变异以及与这些变异相关的疾病，我们现在称之为 TRAPPopathies。
