Basolateral EGF receptor sorting regulated by functionally distinct mechanisms in renal epithelial cells.

摘要: Proliferation of epithelial tissues is controlled by polarized distribution signaling receptors including the EGF receptor (EGFR). In kidney, EGFRs are segregated from soluble ligands present in apical fluid nephrons selective targeting to basolateral membranes. We have shown previously that epithelial-specific clathrin adaptor AP1B mediates EGFR sorting established epithelia. Here we show protein kinase C (PKC)-dependent phosphorylation Thr654 regulates polarity as cells form new cell-cell junctional complexes. The AP1B-dependent pathway does not override a PKC-resistant T654A mutation, and conversely AP1B-defective sort basolaterally PKC-dependent mechanism, polarizing cells. Surprisingly, mutations interfere with these different pathways also produce very distinct phenotypes three-dimensional organotypic cultures. Thus execute functions depending on route. Many renal disorders defects cell notion apically mislocalized promote proliferation still an attractive model explain many aspects polycystic kidney disease. Our data suggest integrates various switching between BL programs developing Fundamental knowledge basic mechanisms governing therefore provides insights into pathogenesis advances drug discovery for disorders.