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PLoS One 2009 Dec 22;412:e8411. doi: 10.1371/journal.pone.0008411.
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A protocadherin-cadherin-FLRT3 complex controls cell adhesion and morphogenesis.

Chen X , Koh E , Yoder M , Gumbiner BM .

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. PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.

PubMed ID: 20027292
PMC ID: PMC2791867
Article link: PLoS One
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: cad cdh1 cdh3 dnai1 dst flrt3 fn1 isyna1 nhs nodal1 pcdh8.2 prss1 rnd1 tgfb1
Antibodies: Cdh3 Ab2 FLAG Ab1 Flrt3 Ab1 Pcdh8.2 Ab1
Morpholinos: flrt1 MO1 flrt3 MO1 flrt3 MO2 pcdh8.2 MO2 pcdh8.2 MO3 rnd1 MO1

Article Images: [+] show captions
References [+] :
Brieher, Regulation of C-cadherin function during activin induced morphogenesis of Xenopus animal caps. 1994, Pubmed, Xenbase