Wnt-11 and Fz7 reduce cell adhesion in convergent extension by sequestration of PAPC and C-cadherin.
Wnt-11/planar cell polarity signaling polarizes mesodermal cells undergoing convergent extension during Xenopus laevis gastrulation. These shape changes associated with lateral intercalation behavior require a dynamic modulation of cell adhesion. In this paper, we report that Wnt-11/frizzled-7 (Fz7) controls cell adhesion by forming separate adhesion-modulating complexes (AMCs) with the paraxial protocadherin (PAPC; denoted as AMCP) and C-cadherin (denoted as AMCC) via distinct Fz7 interaction domains. When PAPC was part of a Wnt-11-Fz7 complex, its Dynamin1- and clathrin-dependent internalization was blocked. This membrane stabilization of AMCP (Fz7/PAPC) by Wnt-11 prevented C-cadherin clustering, resulting in reduced cell adhesion and modified cell sorting activity. Importantly, Wnt-11 did not influence C-cadherin internalization; instead, it promoted the formation of AMCC (Fz7/Cadherin), which competed with cis-dimerization of C-cadherin. Because PAPC and C-cadherin did not directly interact and did not form a joint complex with Fz7, we suggest that Wnt-11 triggers the formation of two distinct complexes, AMCC and AMCP, that act in parallel to reduce cell adhesion by hampering lateral clustering of C-cadherin.
Cell and Developmental Biology, Zoological Institute, Karlsruhe Institute of Technology, 76131 Karlsruhe, Germany.
Bianca
B
Kraft
Corinna D
CD
Berger
Veronika
V
Wallkamm
Herbert
H
Steinbeisser
Doris
D
Wedlich
D000818:Animals; D015820:Cadherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000502:physiology; D005260:Female; D054262:Gastrulation / Q000502:physiology; D046912:Multiprotein Complexes / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000502:physiology; D055503:Protein Multimerization; D000091363:Protocadherins; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D014982:Xenopus laevis
C074260:CDH3 protein, Xenopus; D015820:Cadherins; C492040:Fzd7 protein, Xenopus; D046912:Multiprotein Complexes; C117635:Pcdh8 protein, Xenopus; D000091363:Protocadherins; D043562:Receptors, G-Protein-Coupled; D051153:Wnt Proteins; D029867:Xenopus Proteins; C512785:wnt11b protein, Xenopus