Braun Sigurd, Jentsch Stefan
Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried, Munich D-82152, Germany.
EMBO Rep. 2007 Dec;8(12):1176-82. doi: 10.1038/sj.embor.7401105. Epub 2007 Nov 9.
Endoplasmic reticulum (ER)-associated degradation (ERAD) is a specialized activity of the ubiquitin-proteasome system that is involved in clearing the ER of aberrant proteins and regulating the levels of specific ER-resident proteins. Here we show that the yeast ER-SNARE Ufe1, a syntaxin (Qa-SNARE) involved in ER membrane fusion and retrograde transport from the Golgi to the ER, is prone to degradation by an ERAD-like mechanism. Notably, Ufe1 is protected against degradation through binding to Sly1, a known SNARE regulator of the Sec1-Munc18 (SM) protein family. This mechanism is specific for Ufe1, as the stability of another Sly1 partner, the Golgi Qa-SNARE Sed5, is not influenced by Sly1 interaction. Thus, our findings identify Sly1 as a discriminating regulator of SNARE levels and indicate that Sly1-controlled ERAD might regulate the balance between different Qa-SNARE proteins.
内质网（ER）相关降解（ERAD）是泛素-蛋白酶体系统的一种特殊活动，参与清除内质网中的异常蛋白质并调节特定内质网驻留蛋白的水平。在此我们表明，酵母内质网SNARE蛋白Ufe1，一种参与内质网膜融合以及从高尔基体到内质网逆行转运的 syntaxin（Qa-SNARE），易于通过一种类似ERAD的机制被降解。值得注意的是，Ufe1通过与Sly1结合而免受降解，Sly1是Sec1-Munc18（SM）蛋白家族中一种已知的SNARE调节因子。这种机制对Ufe1具有特异性，因为另一个Sly1的伙伴、高尔基体Qa-SNARE蛋白Sed5的稳定性不受Sly1相互作用的影响。因此，我们的研究结果确定Sly1是SNARE水平的一种区分性调节因子，并表明Sly1控制的ERAD可能调节不同Qa-SNARE蛋白之间的平衡。
