The multi-PDZ domain protein-1 (MUPP-1) expression regulates cellular levels of the PALS-1/PATJ polarity complex

Abstract

MUPP-1 (multi-PDZ domain protein-1) and PATJ (PALS-1-associated tight junction protein) proteins are closely related scaffold proteins and bind to many common interactors including PALS-1 (protein associated with Lin seven) a member of the Crumbs complex. Our goal is to understand how MUPP-1 and PATJ and their interaction with PALS-1 are regulated in the same cells. We have shown that in MCF10A cells there are at least two different and co-existing complexes, PALS-1/MUPP-1 and PALS-1/PATJ. Surprisingly, MUPP-1 levels inversely correlated with PATJ protein levels by acting on the stabilization of the PATJ/PALS-1 complex. Upon MUPP-1 depletion, the increased amounts of PATJ are in part localized at the migrating front of MCF10A cells and are able to recruit more PAR3 (partition defective 3). All together these data indicate that a precise balance between MUPP-1 and PATJ is achieved in epithelial cells by regulating their association with PALS-1.

Keywords: CRB; Crumbs; Dlg1; Drosophila disc large tumor suppressor; Epithelial migration; L27; Lin2/lin7 domain; MUPP-1; PALS; PALS-1-associated tight junction protein; PAR; PATJ; PDZ; Polarity complexes; Protein regulation.; TJ; ZO 1; aPKC; acronym combining the first letters of three proteins: post synaptic density protein (PSD95); atypical protein kinase C; crumbs; multi-PDZ domain protein-1; partition defective; protein associated with Lin seven; tight junction; zonula occludens-1 protein.