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Wnt 通路通过 CED-10/Rac 控制细胞死亡吞噬、纺锤体定向和迁移。

The Wnt pathway controls cell death engulfment, spindle orientation, and migration through CED-10/Rac.

机构信息

Technische Universität Carolo Wilhelmina Braunschweig, Institut für Genetik, Braunschweig, Germany.

出版信息

PLoS Biol. 2010 Feb 2;8(2):e1000297. doi: 10.1371/journal.pbio.1000297.

DOI:10.1371/journal.pbio.1000297
PMID:20126385
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2814829/
Abstract

Wnt signalling pathways have extremely diverse functions in animals, including induction of cell fates or tumours, guidance of cell movements during gastrulation, and the induction of cell polarity. Wnt can induce polar changes in cellular morphology by a remodelling of the cytoskeleton. However, how activation of the Frizzled receptor induces cytoskeleton rearrangement is not well understood. We show, by an in depth 4-D microscopy analysis, that the Caenorhabditis elegans Wnt pathway signals to CED-10/Rac via two separate branches to regulate modulation of the cytoskeleton in different cellular situations. Apoptotic cell clearance and migration of the distal tip cell require the MOM-5/Fz receptor, GSK-3 kinase, and APC/APR-1, which activate the CED-2/5/12 branch of the engulfment machinery. MOM-5 (Frizzled) thus can function as an engulfment receptor in C. elegans. Our epistatic analyses also suggest that the two partially redundant signalling pathways defined earlier for engulfment may act in a single pathway in early embryos. By contrast, rearrangement of mitotic spindles requires the MOM-5/Fz receptor, GSK-3 kinase, and beta-catenins, but not the downstream factors LIT-1/NLK or POP-1/Tcf. Taken together, our results indicate that in multiple developmental processes, CED-10/Rac can link polar signals mediated by the Wnt pathway to rearrangements of the cytoskeleton.

摘要

Wnt 信号通路在动物中具有极其多样化的功能，包括诱导细胞命运或肿瘤、引导原肠胚形成过程中的细胞运动以及诱导细胞极性。Wnt 可以通过细胞骨架的重塑诱导细胞形态的极性变化。然而，Frizzled 受体的激活如何诱导细胞骨架重排尚不清楚。我们通过深入的 4-D 显微镜分析表明，秀丽隐杆线虫 Wnt 途径通过两条独立的分支向 CED-10/Rac 发出信号，以调节不同细胞情况下细胞骨架的调制。凋亡细胞清除和远端尖端细胞的迁移需要 MOM-5/Fz 受体、GSK-3 激酶和 APC/APR-1，它们激活吞噬机制的 CED-2/5/12 分支。因此，MOM-5（Frizzled）可以在秀丽隐杆线虫中作为吞噬受体发挥作用。我们的上位性分析还表明，以前定义的用于吞噬的两个部分冗余信号通路可能在早期胚胎中作用于单个通路。相比之下，有丝分裂纺锤体的重排需要 MOM-5/Fz 受体、GSK-3 激酶和β-连环蛋白，但不需要下游因子 LIT-1/NLK 或 POP-1/Tcf。总之，我们的结果表明，在多种发育过程中，CED-10/Rac 可以将 Wnt 途径介导的极性信号与细胞骨架的重排联系起来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/03e4034ce8be/pbio.1000297.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/7492679ddcff/pbio.1000297.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/3bfbeb79c4be/pbio.1000297.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/49234bce522d/pbio.1000297.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/991f3f0b8ea1/pbio.1000297.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/99cc8b693f56/pbio.1000297.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/4f0cb825c721/pbio.1000297.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/263100251dee/pbio.1000297.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/03e4034ce8be/pbio.1000297.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/7492679ddcff/pbio.1000297.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/3bfbeb79c4be/pbio.1000297.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/49234bce522d/pbio.1000297.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/991f3f0b8ea1/pbio.1000297.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/99cc8b693f56/pbio.1000297.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/4f0cb825c721/pbio.1000297.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/263100251dee/pbio.1000297.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/100a/2814829/03e4034ce8be/pbio.1000297.g008.jpg

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