Membrane-Anchored Hairless Protein Restrains Notch Signaling Activity.
Membrane-Anchored Hairless Protein Restrains Notch Signaling Activity.
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DOI：
10.3390/genes11111315
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发表时间：
2020-11-06
期刊：
影响因子：
3.5
通讯作者：
Maier D
中科院分区：
文献类型：
--
作者：
Maier D
Notch信号通路控制高等真核生物中的细胞间通讯。在果蝇中，跨膜受体Notch裂解后，Notch的胞内结构域（ICN）与无毛抑制因子（Suppressor of Hairless，Su（H））结合并穿梭进入细胞核以激活Notch靶基因。同样，Notch拮抗剂Hairless将Su（H）转移到细胞核中以抑制Notch靶基因。为了防止Su（H）核转位，将Hairless融合到跨膜结构域以将蛋白质锚在膜上。事实上，内源性Su（H）与膜锚定的Hairless共定位，证明它们在细胞质中结合。此外，成体表型揭示了Notch活性的丧失，支持细胞溶质中的膜锚定无毛螯合Su（H）。膜锚定的Hairless与Su（H）的组合过表达导致组织增殖，这与野生型基因异位共过表达后观察到的细胞凋亡相反，表明向获得Notch活性的转变。混合反应，Notch信号传导输出的一般去抑制，加上在最高Notch活性位置的抑制，可能反映了Su（H）作为激活剂和抑制剂的作用，这得到了用无毛结合缺陷Su（H）LLL突变体获得的结果的支持，仅诱导激活。总的来说，结果加强了Su（H）和无毛复合物在胞质隔室内形成的想法。
The Notch signaling pathway governs cell-to-cell communication in higher eukaryotes. In Drosophila, after cleavage of the transmembrane receptor Notch, the intracellular domain of Notch (ICN) binds to the transducer Suppressor of Hairless (Su(H)) and shuttles into the nucleus to activate Notch target genes. Similarly, the Notch antagonist Hairless transfers Su(H) into the nucleus to repress Notch target genes. With the aim to prevent Su(H) nuclear translocation, Hairless was fused to a transmembrane domain to anchor the protein at membranes. Indeed, endogenous Su(H) co-localized with membrane-anchored Hairless, demonstrating their binding in the cytoplasm. Moreover, adult phenotypes uncovered a loss of Notch activity, in support of membrane-anchored Hairless sequestering Su(H) in the cytosol. A combined overexpression of membrane-anchored Hairless with Su(H) lead to tissue proliferation, which is in contrast to the observed apoptosis after ectopic co-overexpression of the wild-type genes, indicating a shift to a gain of Notch activity. A mixed response, general de-repression of Notch signaling output, plus inhibition at places of highest Notch activity, perhaps reflects Su(H)’s role as activator and repressor, supported by results obtained with the Hairless-binding deficient Su(H)LLL mutant, inducing activation only. Overall, the results strengthen the idea of Su(H) and Hairless complex formation within the cytosolic compartment.
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DOI：
10.1038/nrg3272
发表时间：
2012-09
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
影响因子：
14.9
作者：
Käll L;Krogh A;Sonnhammer EL
通讯作者：
Sonnhammer EL
影响因子：
11.4
作者：
Djiane, Alexandre;Krejci, Alena;Bernard, Frederic;Fexova, Silvie;Millen, Katherine;Bray, Sarah J.
通讯作者：
Bray, Sarah J.
影响因子：
2.6
作者：
Fromental-Ramain, Catherine;Taquet, Nathalie;Ramain, Philippe
通讯作者：
Ramain, Philippe
影响因子：
9.8
作者：
Borggrefe T;Oswald F
通讯作者：
Oswald F