401 PP2A-B55α dephosphorylates desmoplakin's C-terminus to regulate cell adhesion

Critical for the maintenance of epidermal stability and function are attachments between intermediate filaments (IF) intercellular junctions called desmosomes. The desmosomal cytoplasmic plaque protein desmoplakin (DP) is essential anchoring IF to junction. DP-IF interactions regulated by a phospho-regulatory motif within DP C-terminus. Previously we showed that hypo-phosphorylated increased interaction strength, impairing desmosome formation due retention on IF, but generated stronger, more stable desmosomes in mature cell sheets. Thus, DP’s phospho-regulation provides mechanism finely tune junction assembly dynamics adhesion strength. Our group identified GSK3b as capable phosphorylating C-terminus; however, phosphatase responsible dephosphorylation was unknown. Protein 2A (PP2A) comprises scaffolding subunit (A), catalytic (C), one 23 different regulatory subunits (B) binding PP2A substrates. Here, identify PP2A-B55a holoenzyme dephosphorylating Using co-immunoprecipitation colocalization analysis demonstrate B55a new partner keratinocytes uncover novel DP-dependent membrane-bound fraction both 2D- 3D- models. Furthermore, show activity increases tissue integrity manner similar expression variant, S2849G DP. Finally, signaling required proper recruitment during vitro vivo embryonic epidermis B55a-deficient mice. Together, our data uncovers potential PP2A-B55a’s regulation association epidermis.