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GLP-1/Notch RAM结构域的突变导致强烈的Glp-1表型。

Mutation of GLP-1/Notch RAM domain results in a strong Glp-1 phenotype.

作者信息

Crittenden Sarah L, Dos Santos Stephany J Costa, Battula Sindhu, Kimble Judith

机构信息

Department of Biochemistry, University of Wisconsin-Madison.

Present: WiCell Research Institute Madison, WI.

出版信息

MicroPubl Biol. 2024 Nov 7;2024. doi: 10.17912/micropub.biology.001391. eCollection 2024.

DOI:10.17912/micropub.biology.001391
PMID:39583580
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11582880/
Abstract

The distal tip cell niche uses GLP-1 /Notch signaling to maintain germline stem cells. The RAM domain, which resides within the intracellular portion of the GLP-1 /Notch receptor, is integral to formation of a signaling-dependent transcription activation complex. Here we report the generation of a mutation in the GLP-1 RAM domain, created in a GLP-1 /Notch receptor with a C-terminal V5 tag. The phenotype of homozygotes is similar to that of null mutants, but expression of the GLP-1 (RAM ) protein was normal in the heterozygotes. We conclude that the RAM mutation abolishes receptor activity.

摘要

远端末梢细胞生态位利用GLP-1/Notch信号通路来维持生殖系干细胞。RAM结构域位于GLP-1/Notch受体的细胞内部分,对于信号依赖的转录激活复合物的形成不可或缺。在此,我们报告了在带有C端V5标签的GLP-1/Notch受体中产生的GLP-1 RAM结构域突变。纯合子的表型与无效突变体相似,但杂合子中GLP-1(RAM )蛋白的表达正常。我们得出结论,RAM突变消除了受体活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f7/11582880/e9d1439782b2/25789430-2024-micropub.biology.001391.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f7/11582880/e9d1439782b2/25789430-2024-micropub.biology.001391.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55f7/11582880/e9d1439782b2/25789430-2024-micropub.biology.001391.jpg

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本文引用的文献

1
Temporal dynamics and stoichiometry in human Notch signaling from Notch synaptic complex formation to nuclear entry of the Notch intracellular domain.人 Notch 信号通路中 Notch 突触复合物形成到 Notch 胞内结构域进入核内的时空动态和化学计量。
Dev Cell. 2024 Jun 3;59(11):1425-1438.e8. doi: 10.1016/j.devcel.2024.03.021. Epub 2024 Apr 3.
2
LST-1 is a bifunctional regulator that feeds back on Notch-dependent transcription to regulate germline stem cells.LST-1 是一种双功能调节剂,通过反馈 Notch 依赖性转录来调节生殖干细胞。
Proc Natl Acad Sci U S A. 2023 Sep 26;120(39):e2309964120. doi: 10.1073/pnas.2309964120. Epub 2023 Sep 20.
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Analysis of the C. elegans Germline Stem Cell Pool.
秀丽隐杆线虫生殖干细胞池分析。
Methods Mol Biol. 2023;2677:1-36. doi: 10.1007/978-1-0716-3259-8_1.
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SALSA, a genetically encoded biosensor for spatiotemporal quantification of Notch signal transduction in vivo.SALSA,一种遗传编码的生物传感器,用于体内时空定量 Notch 信号转导。
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MicroPubl Biol. 2020 Jun 22;2020. doi: 10.17912/micropub.biology.000271.
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PRP-19, a conserved pre-mRNA processing factor and E3 ubiquitin ligase, inhibits the nuclear accumulation of GLP-1/Notch intracellular domain.PRP-19是一种保守的前体mRNA加工因子和E3泛素连接酶,可抑制GLP-1/Notch细胞内结构域的核内积累。
Biol Open. 2018 Jul 16;7(7):bio034066. doi: 10.1242/bio.034066.
9
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Elife. 2016 Oct 5;5:e18370. doi: 10.7554/eLife.18370.
10
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