OSM-11 facilitates LIN-12 Notch signaling during Caenorhabditis elegans vulval development.
OSM-11 facilitates LIN-12 Notch signaling during Caenorhabditis elegans vulval development.
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DOI：
10.1371/journal.pbio.0060196
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发表时间：
2008-08-12
期刊：
影响因子：
9.8
通讯作者：
Hart AC
中科院分区：
文献类型：
--
作者：
Komatsu H;Chao MY;Larkins-Ford J;Corkins ME;Somers GA;Tucey T;Dionne HM;White JQ;Wani K;Boxem M;Hart AC
Notch信号传导对于发育过程中的细胞命运决定至关重要。秀丽隐杆线虫和脊椎动物Notch配体比经典的果蝇Notch配体更多样化，表明可能的功能复杂性。在这里，我们描述了OSM-11在Notch信号传导中的发育作用，OSM-11以前曾与C.优美的我们发现OSM-11的完全缺失导致外阴发育过程中外阴前体细胞（VPC）命运特化的缺陷，这与Notch信号的减少一致。OSM-11是一种分泌的、可扩散的蛋白质，与先前描述的C. elegans Delta、Serrate和LAG-2（DSL）配体可以与谱系缺陷型-12（LIN-12）Notch受体胞外域相互作用。此外，OSM-11和类似的C.线虫蛋白质与来自其它物种的Notch配体在这里定义为Delta和OSM-11（DOS）基序的序列中共享共同的基序。外阴发育中的osm-11功能丧失缺陷由于其他DOS基序基因的丧失或Notch配体DSL-1的丧失而加剧，这表明DOS基序和DSL蛋白在体内共同作用以激活Notch信号传导。哺乳动物DOS基序蛋白Deltalike 1（DLK 1）可以替代C. elegans发育，表明DOS基序功能在物种间是保守的。我们假设C.线虫OSM-11和同源蛋白作为Notch受体的共激活剂，允许在脊椎动物和无脊椎动物的发育程序中精确调节Notch受体信号传导。Notch受体活化的经典观点涉及受体与含有保守DSL（Delta、Serrate和LAG-2）结构域的跨膜Notch配体的结合。在这里，我们发现，秀丽隐杆线虫OSM-11蛋白是一种新的配体的特点Notch信号转导通路，并在细胞命运规范在发展过程中发挥作用。OSM-11是一种分泌的、可扩散的蛋白质，其损失降低体内Notch信号传导。OSM-11和相关的C.线虫蛋白不含DSL结构域，但含有我们命名为DOS（Delta和OSM-11）的保守基序，其也存在于除C外的生物体中已知Notch配体的胞外结构域中。优美的OSM-11的功能性哺乳动物同源物是分泌蛋白Deltalike 1（Dlk 1），也称为前脂肪细胞因子1（PREF 1），其在Notch信号调节肥胖和其他发育决定中起着不明确的作用。这表明Notch配体被分成两个互补的共配体家族，它们在发育环境中一起作用以调节Notch信号传导。除了调节发育外，DOS配体在渗透胁迫和C. elegans的行为，这表明以前未被怀疑的作用Notch信号在物种之间。梭Elegans OSM-11蛋白与DSL配体一起作用以激活细胞命运特化中的Notch信号传导，并定义了潜在的Notch共配体的保守家族。
Notch signaling is critical for cell fate decisions during development. Caenorhabditis elegans and vertebrate Notch ligands are more diverse than classical Drosophila Notch ligands, suggesting possible functional complexities. Here, we describe a developmental role in Notch signaling for OSM-11, which has been previously implicated in defecation and osmotic resistance in C. elegans. We find that complete loss of OSM-11 causes defects in vulval precursor cell (VPC) fate specification during vulval development consistent with decreased Notch signaling. OSM-11 is a secreted, diffusible protein that, like previously described C. elegans Delta, Serrate, and LAG-2 (DSL) ligands, can interact with the lineage defective-12 (LIN-12) Notch receptor extracellular domain. Additionally, OSM-11 and similar C. elegans proteins share a common motif with Notch ligands from other species in a sequence defined here as the Delta and OSM-11 (DOS) motif. osm-11 loss-of-function defects in vulval development are exacerbated by loss of other DOS-motif genes or by loss of the Notch ligand DSL-1, suggesting that DOS-motif and DSL proteins act together to activate Notch signaling in vivo. The mammalian DOS-motif protein Deltalike1 (DLK1) can substitute for OSM-11 in C. elegans development, suggesting that DOS-motif function is conserved across species. We hypothesize that C. elegans OSM-11 and homologous proteins act as coactivators for Notch receptors, allowing precise regulation of Notch receptor signaling in developmental programs in both vertebrates and invertebrates. The classic view of Notch receptor activation involves receptor binding to transmembrane Notch ligands that contain a conserved DSL (Delta, Serrate, and LAG-2) domain. Here, we find that the Caenorhabditis elegans OSM-11 protein is a novel ligand of the well-characterized Notch signal transduction pathway and plays a role in cell fate specification during development. OSM-11 is a secreted, diffusible protein whose loss decreases Notch signaling in vivo. OSM-11 and related C. elegans proteins do not contain a DSL domain, but contain a conserved motif we have named DOS (Delta and OSM-11) that is also found in the extracellular domain of known Notch ligands in organisms other than C. elegans. The functional mammalian homolog of OSM-11 is the secreted protein Deltalike1 (Dlk1), also known as Preadipocyte Factor 1 (PREF1), which plays a poorly defined role in Notch signaling regulating obesity and other developmental decisions. This suggests that Notch ligands are split into two complementary coligand families that act together to regulate Notch signaling in developmental contexts. In addition to regulating development, DOS ligands play roles in osmotic stress and C. elegans behavior, suggesting previously unsuspected roles for Notch signaling across species. The C. elegans OSM-11 protein acts with DSL ligands to activate Notch signaling in cell fate specification and defines a conserved family of potential Notch co-ligands.
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影响因子：
--
作者：
Bray, Sarah J.;Takada, Shuji;Harrison, Emma;Shen, Shing-Chuan;Ferguson-Smith, Anne C.
通讯作者：
Ferguson-Smith, Anne C.
影响因子：
2.7
作者：
Fukushige, T;Hawkins, MG;McGhee, JD
通讯作者：
McGhee, JD
影响因子：
10.5
作者：
FLEMING, RJ;SCOTTGALE, TN;ARTAVANISTSAKONAS, S
通讯作者：
ARTAVANISTSAKONAS, S
DOI：
10.1016/j.bbrc.2005.06.046
发表时间：
2005-08-12
影响因子：
3.1
作者：
Fujimoto, N;Terlizzi, J;Uitto, J
通讯作者：
Uitto, J
影响因子：
64.8
作者：
GREENWALD, I;SEYDOUX, G
通讯作者：
SEYDOUX, G