Plakophilin-3 Is Required for Late Embryonic Amphibian Development, Exhibiting Roles in Ectodermal and Neural Tissues

Abstract

The p120-catenin family has undergone a significant expansion during the evolution of vertebrates, resulting in varied functions that have yet to be discerned or fully characterized. Likewise, members of the plakophilins, a related catenin subfamily, are found throughout the cell with little known about their functions outside the desmosomal plaque. While the plakophilin-3 (Pkp3) knockout mouse resulted in skin defects, we find larger, including lethal effects following its depletion in Xenopus. Pkp3, unlike some other characterized catenins in amphibians, does not have significant maternal deposits of mRNA. However, during embryogenesis, two Pkp3 protein products whose temporal expression is partially complimentary become expressed. Only the smaller of these products is found in adult Xenopus tissues, with an expression pattern exhibiting distinctions as well as overlaps with those observed in mammalian studies. We determined that Xenopus Pkp3 depletion causes a skin fragility phenotype in keeping with the mouse knockout, but more novel, Xenopus tailbud embryos are hyposensitive to touch even in embryos lacking outward discernable phenotypes, and we additionally resolved disruptions in certain peripheral neural structures, altered establishment and migration of neural crest, and defects in ectodermal multiciliated cells. The use of two distinct morpholinos, as well as rescue approaches, indicated the specificity of these effects. Our results point to the requirement of Pkp3 in amphibian embryogenesis, with functional roles in a number of tissue types.

Plakophilin-3 Catenin Associates with the ETV1/ER81 Transcription Factor to Positively Modulate Gene Activity

“…We previously reported the morpholino-directed depletion of Pkp3 (>60% efficiency as shown in Figure 5B of Munoz et al, 2012) in early Xenopus laevis embryos results in altered neural crest establishment, as well as ectodermal fragility, touch hyposensitivity and heart defects [24]. Additionally, it has been reported that ETV1 localizes to neural crest cells during development and that other PEA3-subfamily members have roles in crest formation [51], [56].…”

“…Production of in vitro transcribed RNA was done following previously described methods [24]. Other constructs were reported previously and kindly provided by Dr. L. Shemshedini (Fes3xWT-Luc and MMP1-Luc) and Dr. R. Janknecht (MMP1 −87/−88) [48]–[50].…”

“…While their cytoplasmic functions are less understood, Pkp-catenins are involved in regulating mRNA expression, the trafficking of desmosomal cadherins, and insulin-induced cell proliferation [20]–[23]. In addition to such junctional and cytoplasmic localizations and roles, Pkp-catenins were previously reported in the nucleus in some contexts [6], [24]–[31]. Conceivably, some Pkp-catenin roles might later prove to be analogous to those of the beta- and p120-catenin subfamily members that associate directly with transcription-factors (e.g.…”

Pemphigus vulgaris autoimmune globulin induces Src-dependent tyrosine-phosphorylation of plakophilin 3 and its detachment from desmoglein 3

“…Although a role for Pkp3 as a conventional signalling molecule has not been demonstrated to date, there is mounting evidence to suggest that Pkp3 is actively involved in cellular stress response [3], morphogenesis [20] and cancer progression [21]. Interestingly, loss of juxta-membranous Pkp3 staining after heat shock, together with its expression in stress granules, has been reported previously [3], suggesting that Pkp3 might translocate to the cytosol when the cells are exposed to environmental stress.…”

Desmosomal Cadherins

“…Knockdown of PG in zebrafish gave rise to heart defects at 48 hpf (Martin et al 2009). In Xenopus knockdown of PKP3 caused skin fragility, disruption in peripheral neural structures, altered establishment and migration of neural crest, and defects in ectodermal multiciliated cells (Munoz et al 2012).…”