Department of Cell Biology, Physiology and Immunology, Instituto Maimónides de Investigación Biomédica, University of Córdoba, 14014-Córdoba, Spain.
Gen Comp Endocrinol. 2012 Jan 1;175(1):1-9. doi: 10.1016/j.ygcen.2011.08.017. Epub 2011 Aug 30.
The regulated secretory pathway is a hallmark of endocrine and neuroendocrine cells. This process comprises different sequential steps, including ER-associated protein synthesis, ER-to-Golgi protein transport, Golgi-associated posttranslational modification, sorting and packing of secretory proteins into carrier granules, cytoskeleton-based granule transport towards the plasma membrane and tethering, docking and fusion of granules with specialized releasing zones in the plasma membrane. Each one of these steps is tightly regulated by a large number of factors that function in a spatially and temporarily coordinated fashion. During the past three decades, much effort has been devoted to characterize the precise role of the yet-known proteins participating in the different steps of this process and to identify new regulatory factors in order to obtain a unifying picture of the secretory pathway. In spite of this and given the enormous complexity of the process, certain steps are not fully understood yet and many players remain to be identified. In this review, we offer a summary of the current knowledge on the main molecular mechanisms that govern and ensure the correct release of secretory proteins. In addition, we have integrated the advance on the field made possible by studies carried out in non-mammalian vertebrates, which, although not very numerous, have substantially contributed to acquire a mechanistic understanding of the regulated secretory pathway.
受调控的分泌途径是内分泌和神经内分泌细胞的一个标志。这个过程包括不同的连续步骤，包括内质网相关蛋白的合成、内质网到高尔基体的蛋白运输、高尔基体相关的翻译后修饰、分泌蛋白的分拣和包装到载体颗粒中、基于细胞骨架的颗粒向质膜的运输和连接、颗粒与质膜上专门的释放区的对接、融合。这些步骤中的每一步都受到大量因素的严格调控，这些因素以空间和时间协调的方式发挥作用。在过去的三十年中，人们投入了大量的努力来描述参与这一过程不同步骤的已知蛋白的精确作用，并鉴定新的调节因子，以便对分泌途径获得一个统一的认识。尽管如此，考虑到这个过程的巨大复杂性，某些步骤还没有被完全理解，还有许多参与者有待确定。在这篇综述中，我们总结了目前关于调控分泌蛋白正确释放的主要分子机制的知识。此外，我们还整合了在非哺乳动物脊椎动物中进行的研究所取得的领域进展，尽管这些研究并不多，但它们大大有助于我们对受调控的分泌途径获得机制上的理解。
