Nemo-like kinase 1 (Nlk1) and paraxial protocadherin (PAPC) cooperatively control Xenopus gastrulation through regulation of Wnt/planar cell polarity (PCP) signaling
The Wnt/planar cell polarity (PCP) pathway directs cell migration during vertebrate gastrulation and is essential for proper embryonic development. Paraxial protocadherin (PAPC, Gene Symbol pcdh8.2) is an important activator of Wnt/PCP signaling during Xenopus gastrulation, but how PAPC activity is...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
2017
|
| In: |
Differentiation
Year: 2017, Volume: 93, Pages: 27-38 |
| ISSN: | 1432-0436 |
| DOI: | 10.1016/j.diff.2016.10.002 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1016/j.diff.2016.10.002 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0301468116300743 
|
| Author Notes: | Rahul Kumar, Anja Ciprianidis, Susanne Theiß, Herbert Steinbeißer, Lilian T. Kaufmann |
| Summary: | The Wnt/planar cell polarity (PCP) pathway directs cell migration during vertebrate gastrulation and is essential for proper embryonic development. Paraxial protocadherin (PAPC, Gene Symbol pcdh8.2) is an important activator of Wnt/PCP signaling during Xenopus gastrulation, but how PAPC activity is controlled is incompletely understood. Here we show that Nemo-like kinase 1 (Nlk1), an atypical mitogen-activated protein (MAP) kinase, physically associates with the C-terminus of PAPC. This interaction mutually stabilizes both proteins by inhibiting polyubiquitination. The Nlk1 mediated stabilization of PAPC is essential for Wnt/PCP signaling, tissue separation and gastrulation movements. We identified two conserved putative phosphorylation sites in the PAPC C-terminus that are critical for Nlk1 mediated PAPC stabilization and Wnt/PCP regulation. Intriguingly, the kinase activity of Nlk1 itself was not essential for its cooperation with PAPC, suggesting an indirect regulation for example by impeding a different kinase that promotes protein degradation. Overall these results outline a novel, kinase independent role of Nlk1, wherein Nlk1 regulates PAPC stabilization and thereby controls gastrulation movements and Wnt/PCP signaling during development. |
|---|---|
| Item Description: | Available online 28 October 2016 Gesehen am 09.11.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1432-0436 |
| DOI: | 10.1016/j.diff.2016.10.002 |