PLAC1 Affects Cell to Cell Communication by Interacting with the Desmosome Complex

Introduction: X-linked PLAC1 is highly expressed in placenta during embryogenesis, and when ablated in mice, causes aberrant placental cell layer organization. It is also highly expressed in many types of cancer cell-lines. Although it has been shown that it promotes AKT phosphorylation in cancer cells, the exact mechanism by which it influences placental layer differentiation is unclear.

Methods: To investigate the mechanism of action of PLAC1 we did cell fractionation and immunoprecipitation of the protein and Mass Spectrometry analysis to identify its interaction partners. The associated proteins were directly tested for interactions by co-transfection with PLAC1 and immunoprecipitation. Mutations in the ZP-N domain of PLAC1 were introduced to assess its involvement in the interactions.

Results: We provide evidence that Desmoglein-2 (DSG2), a component of the membrane-associated desmosomal complex, directly interacts with PLAC1. Mutations of cysteines in ZP-N domain disrupt the interaction between PLAC1 and DSG-2.

Discussion: Because desmosomes are responsible for establishing lateral cell-cell junctions, we suggest that direct interaction with the lateral junction protein complex may be implicated in the PLAC1 effects on cell-cell interactions, and thereby on the layer structure of the placenta.