SLY1 and Syntaxin 18 specify a distinct pathway for procollagen VII export from the endoplasmic reticulum.
SLY1 and Syntaxin 18 specify a distinct pathway for procollagen VII export from the endoplasmic reticulum.
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DOI：
10.7554/elife.02784
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发表时间：
2014-05-19
期刊：
影响因子：
7.7
通讯作者：
Malhotra V
中科院分区：
文献类型：
--
作者：
Nogueira C;Erlmann P;Villeneuve J;Santos AJ;Martínez-Alonso E;Martínez-Menárguez JÁ;Malhotra V
TANGO1结合并从内质网(ER)输出前胶原VII.在这项研究中，我们报告了TANGO1的细胞质结构域与SLY1之间的联系，SLY1是膜融合所需的蛋白质。通过siRNA敲除SLY1可以在不影响COPII组分的募集、一般蛋白分泌和含有KDEL的蛋白BIP和ERGIC53的逆行运输的情况下阻止内质网中的前胶原VII.已知SLY1与内质网特异的SNARE蛋白Synaxin 17和18相互作用，然而只有Synaxin 18是VII型前胶原输出所必需的。从内质网出口同样庞大的I型前胶原既不需要SLY1，也不需要Synaxin 18。总之，这些发现揭示了http://dx.doi.org/10.7554/eLife.02784.001在内质网对大块胶原家族成员的分选，并强调了分泌货物存在不同的出口途径，其中一条是由含有SLY1和Synaxin 18的特定SNARE复合体介导的。DOI：TANGO1胶原蛋白是将单个细胞连接在一起构建组织和器官的长蛋白质。它们还为骨骼、肌腱和血管提供力量和弹性。像许多其他蛋白质一样，胶原蛋白是在细胞内产生的：它们在一个称为内质网的隔室中折叠，然后包装并运输到另一个称为高尔基体的隔室。然后，胶原蛋白从高尔基体被引导到它们的最终目的地，通常是细胞的外部。小的蛋白质从内质网运输到高尔基体，这些蛋白质被称为囊泡。然而，目前还不清楚像胶原蛋白这样的大蛋白质是如何在这两个隔室之间运输的。众所周知，一种名为TANGO1的蛋白质需要将一种名为VII型前胶原的胶原蛋白引导到细胞外部。TANGO1与VII型前胶原结合，被认为延迟了VII型前胶原从内质网的释放，因此囊泡可以生长到能够容纳如此庞大的货物的大小。Nogueira，Erlmann等人。现在发现，TANGO1与另一种名为SLY1的蛋白质结合，如果要从内质网输出II型前胶原，这种蛋白质也必须存在。相反，另一种不同类型的胶原--I型胶原--的运输不需要TANGO1或SLY1。SLY1有助于融合包裹参与蛋白质运输的结构的膜--如内质网、高尔基体和小泡--这使得囊泡可以从一个隔室传递到另一个隔室。Nogueira，Erlmann等人。Nogueira，Erlmann等人还发现，另一种蛋白质(称为Synaxin 18)也是出口II型前胶原所必需的。建议VII型胶原的输出涉及TANGO1延迟内质网胶原的释放，以便SLY1和Synaxin 18可以将其他细胞膜融合到不断生长的运输囊泡中。在这项工作之后，下一个挑战是揭示不同类型的胶原蛋白是如何相互分离的，并确定哪些特定的囊泡参与了它们的输出。DOI：http://dx.doi.org/10.7554/eLife.02784.002
TANGO1 binds and exports Procollagen VII from the endoplasmic reticulum (ER). In this study, we report a connection between the cytoplasmic domain of TANGO1 and SLY1, a protein that is required for membrane fusion. Knockdown of SLY1 by siRNA arrested Procollagen VII in the ER without affecting the recruitment of COPII components, general protein secretion, and retrograde transport of the KDEL-containing protein BIP, and ERGIC53. SLY1 is known to interact with the ER-specific SNARE proteins Syntaxin 17 and 18, however only Syntaxin 18 was required for Procollagen VII export. Neither SLY1 nor Syntaxin 18 was required for the export of the equally bulky Procollagen I from the ER. Altogether, these findings reveal the sorting of bulky collagen family members by TANGO1 at the ER and highlight the existence of different export pathways for secretory cargoes one of which is mediated by the specific SNARE complex containing SLY1 and Syntaxin 18. DOI: http://dx.doi.org/10.7554/eLife.02784.001 Collagens are long proteins that join individual cells together to build tissues and organs. They also provide strength and elasticity to bones, tendons, and blood vessels. Like many other proteins, collagens are produced inside cells: they are folded in a compartment called the endoplasmic reticulum, and then packaged and transported to another compartment called the Golgi. Collagens are then directed from the Golgi to their final destination, which is typically the outside of the cell. Small proteins travel from the endoplasmic reticulum to the Golgi inside packages called vesicles. However it is not clear how large proteins like collagens are transported between these two compartments. It is known that a protein called TANGO1 is needed to direct a collagen called Procollagen VII to the outside of the cells. TANGO1 binds to Procollagen VII, and it is thought that TANGO1 delays the release of Procollagen VII from the endoplasmic reticulum, so that the vesicle can grow to a size that is able to accommodate such a bulky cargo. Nogueira, Erlmann et al. have now discovered that TANGO1 binds to another protein called SLY1, and that this protein must also be present if Procollagen VII is to be exported from the endoplasmic reticulum. In contrast, the transport of a different type of collagen—Collagen I—does not require TANGO1 or SLY1. SLY1 helps to fuse the membranes that enclose the structures involved in protein trafficking—such as the endoplasmic reticulum, the Golgi, and the vesicles—and this allows the cargoes of vesicles to pass from one compartment to another. Nogueira, Erlmann et al. also found that a second protein (called Syntaxin 18) is also required for the export of Procollagen VII. Nogueira, Erlmann et al. propose that collagen VII export involves TANGO1 delaying the release of collagen from the endoplasmic reticulum so that SLY1 and Syntaxin 18 can fuse other cellular membranes to the growing transport vesicle. Following this work, the next challenge is to uncover how different types of collagens are separated from each other, and identify which specific vesicles are involved in their export. DOI: http://dx.doi.org/10.7554/eLife.02784.002