Caenorhabditis elegans SEL-5/AAK1 regulates cell migration and cell outgrowth independently of its kinase activity
Abstract
During Caenorhabditis elegans 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 C. elegans 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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files; Source Data files have been provided for Figure 3 and Figure 5.
Article and author information
Author details
Funding
Grantová Agentura České Republiky (16-17966Y)
- Marie Macůrková
Grantová Agentura, Univerzita Karlova (1446218/2018)
- Filip Knop
Akademie Věd České Republiky (Lumina quaeruntur grant LQ200522301)
- Teije Corneel Middelkoop
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Paschalis Kratsios, University of Chicago, United States
Version history
- Received: July 16, 2023
- Accepted: July 19, 2024
- Accepted Manuscript published: July 19, 2024 (version 1)
Copyright
© 2024, Knop et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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