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SEL-5/AAK1 通过独立于其激酶活性调节细胞迁移和细胞外生。

SEL-5/AAK1 regulates cell migration and cell outgrowth independently of its kinase activity.

机构信息

Department of Cell Biology, Faculty of Science, Charles University, Prague, Czech Republic.

Institute of Molecular Genetics, Czech Academy of Sciences, Prague, Czech Republic.

出版信息

Elife. 2024 Jul 19;13:e91054. doi: 10.7554/eLife.91054.

DOI:10.7554/eLife.91054
PMID:39028260
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11333045/
Abstract

During development, multiple cells migrate long distances or extend processes to reach their final position and/or attain proper shape. The Wnt signalling pathway stands out as one of the major coordinators of cell migration or cell outgrowth along the anterior-posterior body axis. The outcome of Wnt signalling is fine-tuned by various mechanisms including endocytosis. In this study, we show that SEL-5, the orthologue of mammalian AP2-associated kinase AAK1, acts together with the retromer complex as a positive regulator of EGL-20/Wnt signalling during the migration of QL neuroblast daughter cells. At the same time, SEL-5 in cooperation with the retromer complex is also required during excretory canal cell outgrowth. Importantly, SEL-5 kinase activity is not required for its role in neuronal migration or excretory cell outgrowth, and neither of these processes is dependent on DPY-23/AP2M1 phosphorylation. We further establish that the Wnt proteins CWN-1 and CWN-2, together with the Frizzled receptor CFZ-2, positively regulate excretory cell outgrowth, while LIN-44/Wnt and LIN-17/Frizzled together generate a stop signal inhibiting its extension.

摘要

在发育过程中，多个细胞会进行长距离迁移或延伸突起以到达最终位置和/或获得适当的形状。Wnt 信号通路是协调细胞迁移或细胞沿前后体轴延伸的主要协调者之一。Wnt 信号的结果通过各种机制进行微调，包括内吞作用。在这项研究中，我们表明，SEL-5 是哺乳动物 AP2 相关激酶 AAK1 的同源物，与逆行体复合物一起作为 EGL-20/Wnt 信号在 QL 神经母细胞子细胞迁移过程中的正调节剂。同时，SEL-5 与逆行体复合物的合作也需要在排泄道细胞延伸过程中。重要的是，SEL-5 激酶活性对于其在神经元迁移或排泄细胞延伸中的作用不是必需的，并且这两个过程都不依赖于 DPY-23/AP2M1 磷酸化。我们进一步确定 Wnt 蛋白 CWN-1 和 CWN-2 与 Frizzled 受体 CFZ-2 一起正向调节排泄细胞的延伸，而 LIN-44/Wnt 和 LIN-17/Frizzled 共同产生抑制其延伸的停止信号。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/19321bb8122b/elife-91054-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/1da7e802554a/elife-91054-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/e1b8bd601b39/elife-91054-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/3609c88471de/elife-91054-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/5f5ee81d1601/elife-91054-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/536543247ccb/elife-91054-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/cb3958bbba42/elife-91054-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/191d6adb2b31/elife-91054-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/262a9de0b334/elife-91054-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/8f04cf755d4d/elife-91054-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/a6f7dc5f2fa9/elife-91054-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/0f9b560af5a2/elife-91054-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/33a2b0cee15a/elife-91054-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/8675fd987ea1/elife-91054-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/19321bb8122b/elife-91054-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/1da7e802554a/elife-91054-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/e1b8bd601b39/elife-91054-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/3609c88471de/elife-91054-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/5f5ee81d1601/elife-91054-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/536543247ccb/elife-91054-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/cb3958bbba42/elife-91054-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/191d6adb2b31/elife-91054-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/262a9de0b334/elife-91054-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/8f04cf755d4d/elife-91054-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/a6f7dc5f2fa9/elife-91054-fig5-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/0f9b560af5a2/elife-91054-fig5-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/33a2b0cee15a/elife-91054-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/8675fd987ea1/elife-91054-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/41cd/11333045/19321bb8122b/elife-91054-fig8.jpg

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