Plakophilin 3 mediates Rap1-dependent desmosome assembly and adherens junction maturation.
Bottom Line: Moreover, Pkp3 forms a complex with Rap1 GTPase, promoting its activation and facilitating desmosome assembly.We show further that Pkp3 deficiency causes disruption of an E-cadherin/Rap1 complex required for adherens junction sealing.These findings reveal Pkp3 as a coordinator of desmosome and adherens junction assembly and maturation through its functional association with Rap1.
Affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.Show MeSH
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Mentions: Because functional interactions between E-cad and Rap1 are critical for the formation of E-cad–based cell–cell junctions (Hogan et al., 2004; Price et al., 2004), we next tested whether Pkp3-deficient cells exhibited altered E-cad distribution at cell–cell borders. In cultures of SCC9 and HaCaT cells maintained in high calcium, E-cad membrane staining appeared less well-sealed compared with controls. Particularly in regions with the most aberrant DP, neighboring cells were connected by filopodial-like projections, sometimes with separation between adjacent cells, consistent with a failure to seal properly (Vasioukhin et al., 2000; Figure 8 and Supplemental Figure S4). This pattern of E-cad was also observed in the dynamic conditions of calcium switch (Figure 8B). We further tested whether the cAMP pathway is involved in Pkp3-dependent E-cad distribution. Treatment of Pkp3KD cells with FSK reverses the E-cad phenotype, whereas inhibiting cAMP production with PROP results in an E-cad pattern similar to that seen in untreated Pkp3KD cells (Figure 8C), suggesting that Pkp3 regulates adherens junctions through cAMP-dependent signaling.
Affiliation: Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611.