A protocadherin-cadherin-FLRT3 complex controls cell adhesion and morphogenesis

• Published in: PloS one Vol. 4; no. 12; p. e8411
• Main Authors: Chen, Xuejun, Koh, Eunjin, Yoder, Michael, Gumbiner, Barry M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.12.2009; Public Library of Science (PLoS)
• Subjects: Animals; Biology; Cadherin; Cadherins; Cadherins - metabolism; Cell Adhesion; Cell adhesion & migration; Cell Biology/Cell Adhesion; Cell Biology/Morphogenesis and Cell Biology; CHO Cells; Cricetinae; Cricetulus; Developmental Biology/Morphogenesis and Cell Biology; Dissociation; Embryo, Nonmammalian - cytology; Embryo, Nonmammalian - metabolism; Embryos; Fibronectin; Fibronectins; Flow Cytometry; Gene Knockdown Techniques; Guanosine triphosphatases; Guanosinetriphosphatase; Health sciences; Humans; Immunoprecipitation; Inhibition; Kinases; Leucine; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - metabolism; Morphogenesis; Neurons; Physiological aspects; Physiology; Protein Binding; Protein Transport; Proteins; Protocadherin; Recruitment; rho GTP-Binding Proteins - metabolism; Signaling; Transforming growth factors; Xenopus; Xenopus laevis - embryology; Xenopus laevis - metabolism; Xenopus Proteins - antagonists & inhibitors; Xenopus Proteins - metabolism; United States > US; Virginia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0008411

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. 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. 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.