SMOC-1 interacts with both BMP and glypican to regulate BMP signaling in C. elegans.
SMOC-1 interacts with both BMP and glypican to regulate BMP signaling in C. elegans.
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DOI：
10.1371/journal.pbio.3002272
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发表时间：
2023-08
期刊：
影响因子：
9.8
通讯作者：
中科院分区：
文献类型：
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分泌型模块化钙结合蛋白（SMOCs）是一种在秀丽隐杆线虫和人类等生物体中发现的保守的基质细胞蛋白。SMOC同源物特征性地含有1或2个细胞外钙结合（EC）结构域和1或2个1型甲状腺球蛋白（TY）结构域。果蝇和非洲爪蟾的SMOC蛋白与细胞表面硫酸乙酰肝素蛋白聚糖（HSPGs）相互作用，对骨形态发生蛋白（BMP）信号通路产生积极和消极的影响。在这项研究中，我们使用了生物化学，结构建模和分子遗传学方法的组合来剖析C中唯一SMOC蛋白的功能。优雅我们表明CeSMOC-1结合硫酸肝素蛋白聚糖GPC 3同系物LON-2/磷脂酰肌醇蛋白聚糖，以及BMP 2/4同系物DBL-1的成熟结构域。此外，CeSMOC-1可以同时结合LON-2/磷脂酰肌醇蛋白聚糖和DBL-1/BMP。CeSMOC-1和LON-2/磷脂酰肌醇蛋白聚糖之间的相互作用由CeSMOC-1的EC结构域特异性介导，而CeSMOC-1和DBL-1/BMP之间的完全相互作用需要全长CeSMOC-1。我们提供了体外生物化学和体内功能证据，证明CeSMOC-1以LON-2/磷脂酰肌醇蛋白聚糖依赖性方式负向和以DBL-1/BMP依赖性方式正向调节BMP信号传导。我们进一步表明，在计算机模拟中，果蝇和脊椎动物SMOC蛋白也可以结合成熟的BMP二聚体。我们的工作为进化上保守的SMOC蛋白如何调节BMP信号提供了机制基础。细胞间的信号传导需要精确控制，以确保正常的发育和体内平衡。这项研究表明，保守的分泌模块钙结合蛋白，SMOC，调节骨形态发生蛋白（BMP）信号在线虫C。elegans通过结合BMP和磷脂酰肌醇蛋白聚糖。
Secreted modular calcium-binding proteins (SMOCs) are conserved matricellular proteins found in organisms from Caenorhabditis elegans to humans. SMOC homologs characteristically contain 1 or 2 extracellular calcium-binding (EC) domain(s) and 1 or 2 thyroglobulin type-1 (TY) domain(s). SMOC proteins in Drosophila and Xenopus have been found to interact with cell surface heparan sulfate proteoglycans (HSPGs) to exert both positive and negative influences on the conserved bone morphogenetic protein (BMP) signaling pathway. In this study, we used a combination of biochemical, structural modeling, and molecular genetic approaches to dissect the functions of the sole SMOC protein in C. elegans. We showed that CeSMOC-1 binds to the heparin sulfate proteoglycan GPC3 homolog LON-2/glypican, as well as the mature domain of the BMP2/4 homolog DBL-1. Moreover, CeSMOC-1 can simultaneously bind LON-2/glypican and DBL-1/BMP. The interaction between CeSMOC-1 and LON-2/glypican is mediated specifically by the EC domain of CeSMOC-1, while the full interaction between CeSMOC-1 and DBL-1/BMP requires full-length CeSMOC-1. We provide both in vitro biochemical and in vivo functional evidence demonstrating that CeSMOC-1 functions both negatively in a LON-2/glypican-dependent manner and positively in a DBL-1/BMP-dependent manner to regulate BMP signaling. We further showed that in silico, Drosophila and vertebrate SMOC proteins can also bind to mature BMP dimers. Our work provides a mechanistic basis for how the evolutionarily conserved SMOC proteins regulate BMP signaling. Cell-cell signaling needs to be precisely controlled to ensure proper development and homeostasis. This study shows that the conserved secreted modular calcium binding protein, SMOC, regulates bone morphogenetic protein (BMP) signaling in the nematode C. elegans by binding to both BMP and glypican.
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DOI：
10.1007/978-1-4939-8904-1_6
发表时间：
2019
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Savage-Dunn C;Gleason RJ;Liu J;Padgett RW
通讯作者：
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影响因子：
9.8
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影响因子：
1.9
作者：
Jamshidi, Javad;Abdollahi, Shokoufeh;Darvish, Hossein
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DOI：
10.4161/worm.23843
发表时间：
2013-07-01
期刊：
Worm
影响因子：
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通讯作者：
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