Developmental Cell
Volume 8, Issue 6, June 2005, Pages 829-841
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Article
Distinct PAR-1 Proteins Function in Different Branches of Wnt Signaling during Vertebrate Development

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Summary

The kinase PAR-1 plays conserved roles in cell polarity. PAR-1 has also been implicated in axis establishment in C. elegans and Drosophila and in Wnt signaling, but its role in vertebrate development is unclear. Here we report that PAR-1 has two distinct and essential roles in axial development in Xenopus mediated by different PAR-1 isoforms. Depletion of PAR-1A or PAR-1BX causes dorsoanterior deficits, reduced Spemann organizer gene expression, and inhibition of canonical Wnt-β-catenin signaling. By contrast, PAR-1BY depletion inhibits cell movements and localization of Dishevelled protein to the cell cortex, processes associated with noncanonical Wnt signaling. PAR-1 phosphorylation sites in Dishevelled are required for this translocation, but not for canonical Wnt signaling. We conclude that PAR-1BY is required in the PCP branch and mediates Dsh membrane localization while PAR-1A and PAR-1BX are essential for canonical signaling to β-catenin, possibly via targets other than Dishevelled.

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3

Present address: Department of Molecular, Cell, and Developmental Biology, Mount Sinai Medical Center, 1 Gustave L. Levy Place, Box 1020, New York, New York 10029.

4

Present address: Department of Craniofacial Development, Kings College London, Floor 28, Guy’s Tower, Guy’s Hospital, London SE1 9RT, United Kingdom.