A Fungal Sarcolemmal Membrane-Associated Protein (SLMAP) Homolog Plays a Fundamental Role in Development and Localizes to the Nuclear Envelope, Endoplasmic Reticulum, and Mitochondria
A Fungal Sarcolemmal Membrane-Associated Protein (SLMAP) Homolog Plays a Fundamental Role in Development and Localizes to the Nuclear Envelope, Endoplasmic Reticulum, and Mitochondria
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DOI：
10.1128/ec.00241-14
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发表时间：
2015-04-01
期刊：
影响因子：
--
通讯作者：
Teichert, Ines
中科院分区：
文献类型：
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作者：
Nordzieke, Steffen;Zobel, Thomas;Teichert, Ines
肌膜相关蛋白(SLMAP)是一种尾部锚定蛋白，参与成肌细胞融合、细胞周期进展和染色体遗传等基本细胞过程。此外，SLMAP的错误表达与糖尿病和癌症的内皮功能障碍有关。SLMAP是酵母、丝状真菌、昆虫和哺乳动物中特定信号通路所需的保守的条纹蛋白相互作用磷酸酶和激酶复合体(STRIPAK)的一部分。在丝状真菌中，STRIPAK最初是在大孢子菌中发现的，这是一个真菌分化的模式系统。在这里，我们从功能上描述了STRIPAK亚基PRO45，它是人类SLMAP的同源物。我们证明PRO45是有性繁殖和细胞间融合所必需的，并且它的叉头相关(FHA)结构域在这些过程中是必不可少的。蛋白质-蛋白质相互作用研究表明，PRO45与STRIPAK亚基PRO11和SmMOB3结合，这也是有性繁殖所必需的。超分辨结构照明显微镜(SIM)进一步证实PRO45定位于核膜、内质网和线粒体。SIM还表明，定位到核膜需要STRIPAK亚基PRO11和PRO22，而对于线粒体则不需要。综上所述，我们的研究为真菌SLMAP同源物PRO45的基本作用提供了重要的见解，并提出了STRIPAK相关和STRIPAK无关的功能。
Sarcolemmal membrane-associated protein (SLMAP) is a tail-anchored protein involved in fundamental cellular processes, such as myoblast fusion, cell cycle progression, and chromosomal inheritance. Further, SLMAP misexpression is associated with endothelial dysfunctions in diabetes and cancer. SLMAP is part of the conserved striatin-interacting phosphatase and kinase (STRIPAK) complex required for specific signaling pathways in yeasts, filamentous fungi, insects, and mammals. In filamentous fungi, STRIPAK was initially discovered in Sordaria macrospora, a model system for fungal differentiation. Here, we functionally characterize the STRIPAK subunit PRO45, a homolog of human SLMAP. We show that PRO45 is required for sexual propagation and cell-to-cell fusion and that its forkhead-associated (FHA) domain is essential for these processes. Protein-protein interaction studies revealed that PRO45 binds to STRIPAK subunits PRO11 and SmMOB3, which are also required for sexual propagation. Superresolution structured-illumination microscopy (SIM) further established that PRO45 localizes to the nuclear envelope, endoplasmic reticulum, and mitochondria. SIM also showed that localization to the nuclear envelope requires STRIPAK subunits PRO11 and PRO22, whereas for mitochondria it does not. Taken together, our study provides important insights into fundamental roles of the fungal SLMAP homolog PRO45 and suggests STRIPAK-related and STRIPAK-unrelated functions.