title: Deglycosylation of Na+/K+-ATPase causes the basolateral protein to undergo apical targeting in polarized hepatic cells.
abstract: Polarized epithelia, such as hepatocytes, target their integral membrane proteins to specific apical or basolateral membrane domains during or after biogenesis. The roles played by protein glycosylation in this sorting process remain controversial. We report here that deglycosylation treatments in well-polarized hepatic cells by deglycosylation drugs, or by site-directed mutagenesis of the N-linked-glycosylation residues, all cause the Na+/K+-ATPase beta-subunit to traffic from the native basolateral to the apical/canalicular domain. Deglycosylated beta-subunits are still able to bind and therefore transport the catalytic alpha-subunits to the aberrant apical location. Such apical targeting is mediated via the indirect transcytosis pathway. Cells containing apical Na+/K+-ATPase appear to be defective in maintaining the ionic gradient across the plasma membrane and in executing hepatic activities that are dependent upon the ionic homeostasis such as canalicular excretion.
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, 155 Sec. 2 Linong Street, Taipei 112, Taiwan.
authors.forename: Wei-Nan
authors.initials: WN
authors.lastname: Lian
authors.forename: Tzu-Wei
authors.initials: TW
authors.lastname: Wu
authors.forename: Ro-Lan
authors.initials: RL
authors.lastname: Dao
authors.forename: Yann-Jang
authors.initials: YJ
authors.lastname: Chen
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002460:Cell Line; D016764:Cell Polarity; D006031:Glycosylation; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D016297:Mutagenesis, Site-Directed; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D021122:Protein Subunits; D014415:Tunicamycin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase