Mink1 regulates β-catenin-independent Wnt signaling via Prickle phosphorylation.
β-Catenin-independent Wnt signaling pathways have been implicated in the regulation of planar cell polarity (PCP) and convergent extension (CE) cell movements. Prickle, one of the core proteins of these pathways, is known to asymmetrically localize proximally at the adherens junction of Drosophila melanogaster wing cells and to locally accumulate within plasma membrane subdomains in cells undergoing CE movements during vertebrate development. Using mass spectrometry, we have identified the Ste20 kinase Mink1 as a Prickle-associated protein and found that they genetically interact during the establishment of PCP in the Drosophila eye and CE in Xenopus laevis embryos. We show that Mink1 phosphorylates Prickle on a conserved threonine residue and regulates its Rab5-dependent endosomal trafficking, a process required for the localized plasma membrane accumulation and function of Prickle. Mink1 also was found to be important for the clustering of Vangl within plasma membrane puncta. Our results provide a link between Mink and the Vangl-Prickle complex and highlight the importance of Prickle phosphorylation and endosomal trafficking for its function during Wnt-PCP signaling.
Department of Pharmaceutical Sciences, University of Toronto, Toronto, Canada.
Avais M
AM
Daulat
Olivia
O
Luu
Anson
A
Sing
Liang
L
Zhang
Jeffrey L
JL
Wrana
Helen
H
McNeill
Rudolf
R
Winklbauer
Stéphane
S
Angers
D000595:Amino Acid Sequence; D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000378:metabolism; D060588:LIM Domain Proteins / Q000032:analysis / Q000378:metabolism*; D008565:Membrane Proteins / Q000032:analysis / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000378:metabolism*; D021381:Protein Transport; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D014981:Xenopus / Q000196:embryology / Q000378:metabolism; D029867:Xenopus Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D008565:Membrane Proteins; C515173:PRICKLE1 protein, human; D025521:Tumor Suppressor Proteins; C468513:VANGL2 protein, human; D051153:Wnt Proteins; D029867:Xenopus Proteins; D051176:beta Catenin; C497353:MINK1 protein, human; D017346:Protein Serine-Threonine Kinases