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 basolateral membrane of most epithelial cells in vivo and in cell lines used to study membrane protein sorting. The goal of this study was to define the molecular basis of polar EGFR membrane expression using the Madin-Darby canine kidney cell model. We have identified a 23-amino acid segment located near the cytoplasmic face of the membrane spanning domain (residues Lys-652 to Ala-674) that is necessary and sufficient for targeting EGFRs from the trans-Golgi network directly to the basolateral plasma membrane. Furthermore, the sequence between residues Lys-652 and Ala-674 is sufficient to direct the extracellular domain of an apical membrane protein, decay accelerating factor, to the basolateral membrane. In the absence of this cytoplasmic basolateral sorting signal, information within the extracellular ligand binding domain is sufficient to target EGFRs from the trans-Golgi network directly to the apical 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 helical structure, leading us to postulate that hydrophobic and/or electrostatic interactions may be important for activity of this autonomous basolateral sorting determinant.
Hobert
M E
ME
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.
Kil
S J
SJ
Medof
M E
ME
Carlin
C R
CR
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D016764:Cell Polarity; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D004285:Dogs; D066246:ErbB Receptors / Q000737:chemistry*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008969:Molecular Sequence Data; D014443:Tyrosine / Q000032:analysis
D014443:Tyrosine; D066246:ErbB Receptors