Abstract:
To function properly, neurons must maintain a proteome that differs in their somatodendritic and axonal domain. This requires the polarized sorting of newly synthesized secretory and transmembrane proteins into different vesicle populations as they traverse the secretory pathway. Although the trans-Golgi-network is generally considered to be the main sorting hub, this sorting process may already begin at the ER and continue through the Golgi cisternae. At each step in the sorting process, specificity is conferred by adaptors, GTPases, tethers, and SNAREs. Besides this, local synthesis and unconventional protein secretion may contribute to the polarized proteome to enable rapid responses to stimuli. For some transmembrane proteins, some of the steps in the sorting process are well-studied. These will be highlighted here. The universal rules that govern polarized protein sorting remain unresolved, therefore we emphasize the need to approach this problem in an unbiased, top-down manner. Unraveling these rules will contribute to our understanding of neuronal development and function in health and disease.
摘要:
为了正常工作,神经元必须保持一个蛋白质组,在他们的体树突和轴突结构域不同。这需要将新合成的分泌蛋白和跨膜蛋白极化分选到不同的囊泡群体中,因为它们穿过分泌途径。尽管跨高尔基网络通常被认为是主要的分拣中心,此分选过程可能已经在急诊室开始,并继续通过高尔基池。在排序过程的每个步骤中,特异性由衔接子赋予,GTPases,系绳,和SNARE。除此之外,局部合成和非常规蛋白质分泌可能有助于极化的蛋白质组,以使对刺激的快速反应。对于一些跨膜蛋白,排序过程中的一些步骤得到了很好的研究。这些将在这里强调。控制极化蛋白质分选的通用规则仍未解决,因此,我们强调需要无偏见地解决这个问题,自上而下的方式。解开这些规则将有助于我们对健康和疾病中神经元发育和功能的理解。