THE CYTOPLASMIC JUXTAMEMBRANE DOMAIN OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR CONTAINS A NOVEL AUTONOMOUS BASOLATERAL SORTING DETERMINANT

The epidermal growth factor receptor (EGFR) is localized at the basola teral membrane of most epithelial cells in vivo and in cell lines used to study membrane protein sorting. The goal of this study was to defi ne the molecular basis of polar EGFR membrane expression using the Mad in-Darby canine kidney cell model. We have identified a 23-amino acid segment located near the cytoplasmic face of the membrane spanning dom ain (residues Lys-652 to Ala-674) that is necessary and sufficient for targeting EGFRs from the trans-Golgi network directly to the basolate ral plasma membrane. Furthermore, the sequence between residues Lys-65 2 and Ala-674 is sufficient to direct the extracellular domain of an a pical membrane protein, decay accelerating factor, to the basolateral membrane. In the absence of this cytoplasmic basolateral sorting signa l, information within the extracellular ligand binding domain is suffi cient to target EGFRs from the trans-Golgi network directly to the api cal plasma membrane. The EGFR basolateral sorting determinant does not have sequence and structural requirements common to most basolateral membrane proteins and does not overlap any of the known EGFR endocytic signals, This 23-residue sequence lies in a predicted amphipathic hel ical structure, leading us to postulate that hydrophobic and/or electr ostatic interactions may be important for activity of this autonomous basolateral sorting determinant.