Golgi apparatus and epithelial cell polarity: Lessons from 3 decades of MDCK cells

Abstract

The MDCK model, introduced three decades ago (Cereijido et al. 1978; Rodriguez-Boulan et al. 1978; Rodriguez-Boulan and Pendergast 1980), allowed the elucidation of biosynthetic and recycling routes of epithelial cells and the compartments that sort apical and basolateral proteins as the trans Golgi network (TGN) and recycling endosomes (RE). These compartments were originally believed to operate in separate biosynthetic and recycling routes but discoveries over the past decade have revealed that TGN and RE cooperate in biosynthetic protein sorting. TGN and RE display clathrin-dependent and clathrin-independent exocytic routes to the plasma membrane (PM), equivalent to the clathrin-dependent and clathrin-independent endocytic routes at the PM. In epithelial cells, clathrin-mediated exocytosis (CME) from TGN and RE is utilized only by basolateral PM proteins. With the exception of AP1B, which sorts a subgroup of basolateral proteins in RE, the clathrin adaptors and regulatory proteins involved in CME remain largely unknown. The clathrin-independent routes from TGN and RE to the apical membrane remain enigmatic; their generation involves a clustering event mediated by proteinaceous motifs or by N- or O-linked carbohydrates, which may or may not promote lipid raft association, as well as the key participation of the MT and actin cytoskeletons.