A protocadherin-cadherin-FLRT3 complex controls cell adhesion and morphogenesis.
BACKGROUND
Paraxial protocadherin (PAPC) and fibronectin leucine-rich domain transmembrane protein-3 (FLRT3) are induced by TGFbeta signaling in Xenopus embryos and both regulate morphogenesis by inhibiting C-cadherin mediated cell adhesion.


RESULTS
We have investigated the functional and physical relationships between PAPC, FLRT3, and C-cadherin. Although neither PAPC nor FLRT3 are required for each other to regulate C-cadherin adhesion, they do interact functionally and physically, and they form a complex with cadherins. By itself PAPC reduces cell adhesion physiologically to induce cell sorting, while FLRT3 disrupts adhesion excessively to cause cell dissociation. However, when expressed together PAPC limits the cell dissociating and tissue disrupting activity of FLRT3 to make it effective in physiological cell sorting. PAPC counteracts FLRT3 function by inhibiting the recruitment of the GTPase RND1 to the FLRT3 cytoplasmic domain.


CONCLUSIONS
PAPC and FLRT3 form a functional complex with cadherins and PAPC functions as a molecular "governor" to maintain FLRT3 activity at the optimal level for physiological regulation of C-cadherin adhesion, cell sorting, and morphogenesis.
Chen
Xuejun
X
Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA.
Koh
Eunjin
E
Yoder
Michael
M
Gumbiner
Barry M
BM
D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D006224:Cricetinae; D003412:Cricetulus; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009024:Morphogenesis; D011485:Protein Binding; D021381:Protein Transport; D000091363:Protocadherins; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology* / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
C074260:CDH3 protein, Xenopus; D015820:Cadherins; C542073:FLRT3 protein, Xenopus; D008565:Membrane Proteins; C117635:Pcdh8 protein, Xenopus; D000091363:Protocadherins; C491770:Rnd1 protein, Xenopus; D029867:Xenopus Proteins; D020741:rho GTP-Binding Proteins