Robinson David G, Pimpl Peter
Centre for Organismal Studies (COS), University of Heidelberg, Heidelberg, Germany.
Protoplasma. 2014 Jan;251(1):247-64. doi: 10.1007/s00709-013-0542-7. Epub 2013 Sep 10.
In this article we challenge the widely accepted view that receptors for soluble vacuolar proteins (VSRs) bind to their ligands at the trans-Golgi network (TGN) and transport this cargo via clathrin-coated vesicles (CCV) to a multivesicular prevacuolar compartment. This notion, which we term the "classical model" for vacuolar protein sorting, further assumes that low pH in the prevacuolar compartment causes VSR-ligand dissociation, resulting in a retromer-mediated retrieval of the VSRs to the TGN. We have carefully evaluated the literature with respect to morphology and function of the compartments involved, localization of key components of the sorting machinery, and conclude that there is little direct evidence in its favour. Firstly, unlike mammalian cells where the sorting receptor for lysosomal hydrolases recognizes its ligand in the TGN, the available data suggests that in plants VSRs interact with vacuolar cargo ligands already in the endoplasmic reticulum. Secondly, the evidence supporting the packaging of VSR-ligand complexes into CCV at the TGN is not conclusive. Thirdly, the prevacuolar compartment appears to have a pH unsuitable for VSR-ligand dissociation and lacks the retromer core and the sorting nexins needed for VSR recycling. We present an alternative model for protein sorting in the TGN that draws attention to the much overlooked role of Ca(2+) in VSR-ligand interactions and which may possibly also be a factor in the sequestration of secretory proteins.
在本文中，我们对一种广泛接受的观点提出质疑，该观点认为可溶性液泡蛋白受体（VSRs）在反式高尔基体网络（TGN）与它们的配体结合，并通过网格蛋白包被囊泡（CCV）将这种货物运输到多泡前液泡区室。我们将这种观点称为液泡蛋白分选的“经典模型”，它还进一步假定前液泡区室中的低pH值会导致VSR-配体解离，从而导致VSRs通过回收体介导的方式被运回TGN。我们仔细评估了关于所涉及区室的形态和功能、分选机制关键成分的定位等方面的文献，并得出结论，几乎没有直接证据支持这一观点。首先，与哺乳动物细胞中溶酶体水解酶的分选受体在TGN中识别其配体不同，现有数据表明在植物中VSRs在内质网中就已经与液泡货物配体相互作用。其次，支持VSR-配体复合物在TGN被包装进CCV的证据并不确凿。第三，前液泡区室的pH值似乎不适合VSR-配体解离，并且缺乏VSR回收所需的回收体核心和分选连接蛋白。我们提出了一种TGN中蛋白质分选的替代模型，该模型提请人们注意Ca(2+)在VSR-配体相互作用中被大大忽视的作用，并且这可能也是分泌蛋白隔离的一个因素。
