SMOC-1与BMP和glypian相互作用以调节秀丽隐杆线虫中的BMP信号传导。

IF 7.8 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
PLoS Biology Pub Date : 2023-08-17 eCollection Date: 2023-08-01 DOI:10.1371/journal.pbio.3002272
Melisa S DeGroot, Byron Williams, Timothy Y Chang, Maria L Maas Gamboa, Isabel M Larus, Garam Hong, J Christopher Fromme, Jun Liu
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引用次数: 0

摘要

分泌模块化钙结合蛋白(SMOC)是从秀丽隐杆线虫到人类等生物体中发现的保守基质细胞蛋白。SMOC同源物特征性地包含1或2个细胞外钙结合(EC)结构域和1或2种甲状腺球蛋白1型(TY)结构域。果蝇和爪蟾中的SMOC蛋白已被发现与细胞表面硫酸乙酰肝素蛋白多糖(HSPGs)相互作用,对保守的骨形态发生蛋白(BMP)信号通路产生积极和消极的影响。在这项研究中,我们结合生物化学、结构建模和分子遗传学方法来剖析秀丽隐杆线虫中唯一SMOC蛋白的功能。我们发现CeSMOC-1与肝素硫酸盐蛋白聚糖GPC3同源物LON-2/glypian以及BMP2/4同源物DBL-1的成熟结构域结合。此外,CeSMOC-1可以同时结合LON-2/glypian和DBL-1/BMP。CeSMOC-1和LON-2/glypian之间的相互作用是由CeSMOC1的EC结构域特异性介导的,而CeSMOC-11和DBL-1/BMP之间的完全相互作用需要全长的CeSMOC.1。我们提供了体外生物化学和体内功能证据,证明CeSMOC-1在调节BMP信号传导方面既以LON-2/glypian依赖的方式负向发挥作用,又以DBL-1/BMP依赖的方式正向发挥作用。我们进一步证明,在计算机中,果蝇和脊椎动物的SMOC蛋白也可以与成熟的BMP二聚体结合。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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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.

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.

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.

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来源期刊
PLoS Biology
PLoS Biology 生物-生化与分子生物学
CiteScore
14.40
自引率
2.00%
发文量
359
审稿时长
3 months
期刊介绍: PLOS Biology is an open-access, peer-reviewed general biology journal published by PLOS, a nonprofit organization of scientists and physicians dedicated to making the world's scientific and medical literature freely accessible. The journal publishes new articles online weekly, with issues compiled and published monthly. ISSN Numbers: eISSN: 1545-7885 ISSN: 1544-9173
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