Mouse Stbd1 is N-myristoylated and affects ER-mitochondria association and mitochondrial morphology.
Mouse Stbd1 is N-myristoylated and affects ER-mitochondria association and mitochondrial morphology.
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DOI：
10.1242/jcs.195263
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发表时间：
2017-03-01
影响因子：
4
通讯作者：
Petrou PP
中科院分区：
文献类型：
--
作者：
Demetriadou A;Morales-Sanfrutos J;Nearchou M;Baba O;Kyriacou K;Tate EW;Drousiotou A;Petrou PP
淀粉结合结构域蛋白1(Stbd1)是一种碳水化合物结合蛋白，是糖原的选择性自噬受体。在这里，我们证明了小鼠Stbd1是一种跨膜内质网(ER)驻留蛋白，具有诱导HeLa细胞形成有组织的ER结构的能力。除了大块内质网外，Stbd1还定位于线粒体相关膜(MAM)，线粒体相关膜代表内质网和线粒体之间的紧密结合区域。我们证明N-肉豆蔻基化和Stbd1与糖原的结合是其亚细胞靶向的主要决定因素。此外，非肉豆蔻酰化Stbd1的过表达增强了内质网与线粒体之间的联系，并进一步诱导了显著的线粒体碎裂和聚集。相反，shRNA介导的Stbd1沉默导致内质网和线粒体之间的间距增加，并改变了线粒体网络的形态，表明线粒体的融合和相互连接增加。我们的数据揭示了Stbd1亚细胞靶向的分子机制，支持并扩展了其作为糖原选择性自噬受体的功能，并揭示了该蛋白在内质网和线粒体之间的物理联系中的新作用。糖原结合蛋白Stbd1是N-肉豆蔻酰化的，定位于内质网-线粒体接触部位。Stbd1功能丧失或获得影响内质网-线粒体结合和线粒体形态。
Starch binding domain-containing protein 1 (Stbd1) is a carbohydrate-binding protein that has been proposed to be a selective autophagy receptor for glycogen. Here, we show that mouse Stbd1 is a transmembrane endoplasmic reticulum (ER)-resident protein with the capacity to induce the formation of organized ER structures in HeLa cells. In addition to bulk ER, Stbd1 was found to localize to mitochondria-associated membranes (MAMs), which represent regions of close apposition between the ER and mitochondria. We demonstrate that N-myristoylation and binding of Stbd1 to glycogen act as major determinants of its subcellular targeting. Moreover, overexpression of non-myristoylated Stbd1 enhanced the association between ER and mitochondria, and further induced prominent mitochondrial fragmentation and clustering. Conversely, shRNA-mediated Stbd1 silencing resulted in an increase in the spacing between ER and mitochondria, and an altered morphology of the mitochondrial network, suggesting elevated fusion and interconnectivity of mitochondria. Our data unravel the molecular mechanism underlying Stbd1 subcellular targeting, support and expand its proposed function as a selective autophagy receptor for glycogen and uncover a new role for the protein in the physical association between ER and mitochondria. The glycogen-binding protein Stbd1 is N-myristoylated and targeted to ER–mitochondria contact sites. Stbd1 loss- or gain-of-function affects ER–mitochondria association and mitochondrial morphology.