%0 Generic
%A Berger, Corinna D.
%D 2009
%F heidok:9792
%K Proteininteraktion , Wnt-Signalwege , Paraxial Protocadheringastrulation , Paraxial Protocadherin , cell adhesion , wnt signaling , protein interaction
%R 10.11588/heidok.00009792
%T Regulation of Morphogenetic Cell Behavior by Xenopus Paraxial Protocadherin
%U https://archiv.ub.uni-heidelberg.de/volltextserver/9792/
%X Gastrulation is one of the most important processes during embryogenesis and must therefore be strictly controlled. A central regulator of this complex morphogenetic process is Paraxial Protocadherin (PAPC). PAPC function is necessary for convergent extension movements and tissue separation. It promotes beta-catenin-independent Wnt-signaling and modulates C-Cadherin-mediated cell adhesion.  In this work I explored the role of PAPC in convergent extension and tissue separation. I could show using loss of function approaches that PAPC is necessary for the elongated cell shape and the bipolarity of mesodermal cells. Furthermore the activation of endogenous Rho, which can be visualized by a novel in situ staining method, depends on PAPC in the dorsal marginal zone. PAPC promotes the activation of Rho by antagonizing Spry, an inhibitor of beta-catenin-independent Wnt-signaling, by binding to it. The interaction between PAPC and Spry is independent of FGF signaling, but the two putative phosphorylation sites at serines 741 and 955 in the cytoplasmic domain of PAPC are essential for it. The expression of the PAPC cytoplasmic domain alone but not of the point mutant PAPC-S741A/S955A, which is unable to bind to Spry, can rescue Rho activation after PAPC loss of function. In addition the cytoplasmic domain of PAPC can enter the nucleus, where it might mediate transcription.  Using bimolecular fluorescence complementation I could show that PAPC interacts with C-Cadherin and the receptor Frizzled 7 (Fz7). In gain of function experiments PAPC decreases cell adhesion by binding to C-Cadherin. For this function only the extracellular and transmembrane domains of PAPC are necessary. Although PAPC induces endocytosis of C-Cadherin/PAPC-complexes in intact tissues, this effect does not contribute to the downregulation of cell adhesion. PAPC interacts with Fz7 via their extracellular domains. PAPC and Fz7 do not act as ligand and receptor across cell membranes; both proteins must be inside the same cell in order to induce ectopic tissue separation in the ectoderm. Furthermore the interaction between PAPC and Fz7 can be modulated by coexpression of C-Cadherin or Wnt11, a ligand of Fz7.