A catenin of the plakophilin-subfamily, Pkp3, responds to canonical-Wnt pathway components and signals.
A catenin of the plakophilin-subfamily, Pkp3, responds to canonical-Wnt pathway components and signals.
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DOI：
10.1016/j.bbrc.2021.05.043
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发表时间：
2021-07-23
影响因子：
3.1
通讯作者：
McCrea PD
中科院分区：
文献类型：
--
作者：
Hong JY;Zapata J;Blackburn A;Baumert R;Bae SM;Ji H;Nam HJ;Miller RK;McCrea PD
脊椎动物β -连环蛋白作为典型wnt信号的换能器起着关键作用。我们之前报道过，与β -连环蛋白类似，p120-连环蛋白异构体的细胞质信号池在响应经典wnt信号时是稳定的。为了更广泛地了解wnt通路对连环蛋白的影响，我们将重点放在作为plakophilin-catenin亚家族代表的plakophilin-3 （plakophilin-3; Pkp3）上。亲血小板蛋白促进组织完整性，协助桥粒体钙粘蛋白连接到桥粒连接处的中间丝，并且与其他连环蛋白一样，它们在细胞核内执行其他功能。在本报告中，我们测试了经典wnt通路成分是否调节Pkp3蛋白水平。我们发现，与β -连环蛋白和p120-连环蛋白异构体一样，Pkp3在wnt配体或LRP6受体的显性活性形式存在下是稳定的。在表达破坏复合物组分如GSK3β和Axin时，Pkp3的水平相反地降低，并且与β -连环蛋白和p120-isoform1进一步相似，Pkp3与GSK3β和Axin相关。最后，我们注意到pkp3 -连环蛋白在响应Wnt配体时跨位进入细胞核，并刺激一个被接受的Wnt报告蛋白。这些发现符合上下文相关的wnt信号或通路成分调节pkp3 -连环蛋白水平的扩展模型。未来的研究将需要评估潜在的基因调控、细胞粘附或细胞骨架效应。
Vertebrate beta-catenin plays a key role as a transducer of canonical-Wnt signals. We earlier reported that, similar to beta-catenin, the cytoplasmic signaling pool of p120-catenin-isoform1 is stabilized in response to canonical-Wnt signals. To obtain a yet broader view of the Wnt-pathway’s impact upon catenin proteins, we focused upon plakophilin3 (plakophilin-3; Pkp3) as a representative of the plakophilin-catenin subfamily. Promoting tissue integrity, the plakophilins assist in linking desmosomal cadherins to intermediate filaments at desmosome junctions, and in common with other catenins they perform additional functions including in the nucleus. In this report, we test whether canonical-Wnt pathway components modulate Pkp3 protein levels. We find that in common with beta-catenin and p120-catenin-isoform1, Pkp3 is stabilized in the presence of a Wnt-ligand or a dominant-active form of the LRP6 receptor. Pkp3’s levels are conversely lowered upon expressing destruction-complex components such as GSK3β and Axin, and in further likeness to beta-catenin and p120-isoform1, Pkp3 associates with GSK3beta and Axin. Finally, we note that Pkp3-catenin trans-localizes into the nucleus in response to Wnt-ligand and stimulates an accepted Wnt reporter. These findings fit an expanded model where context-dependent Wnt-signals or pathway components modulate Pkp3-catenin levels. Future studies will be needed to assess potential gene regulatory, cell adhesive, or cytoskeletal effects.
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DOI：
10.1073/pnas.96.11.6273
发表时间：
1999-05-25
影响因子：
11.1
作者：
Liu, CM;Kato, Y;He, X
通讯作者：
He, X
影响因子：
4.3
作者：
Keil, Rene;Wolf, Annika;Hatzfeld, Mechthild
通讯作者：
Hatzfeld, Mechthild
影响因子：
7.2
作者：
MacDonald, Bryan T.;He, Xi
通讯作者：
He, Xi
影响因子：
1.5
作者：
Li J;Radice GL
通讯作者：
Radice GL
DOI：
10.1083/jcb.200402153
发表时间：
2004-10-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gottardi CJ;Gumbiner BM
通讯作者：
Gumbiner BM