title: Membrane proteins follow multiple pathways to the basolateral cell surface in polarized epithelial cells.
abstract: Newly synthesized apical and basolateral membrane proteins are sorted from one another in polarized epithelial cells. The trans-Golgi network participates in this sorting process, but some basolateral proteins travel from the Golgi to recycling endosomes (REs) before their surface delivery. Using a novel system for pulse-chase microscopy, we have visualized the postsynthetic route pursued by a newly synthesized cohort of Na,K-ATPase. We find that the basolateral delivery of newly synthesized Na,K-ATPase occurs via a pathway distinct from that pursued by the vesicular stomatitis virus G protein (VSV-G). Na,K-ATPase surface delivery occurs at a faster rate than that observed for VSV-G. The Na,K-ATPase does not pass through the RE compartment en route to the plasma membrane, and Na,K-ATPase trafficking is not regulated by the same small GTPases as other basolateral proteins. Finally, Na,K-ATPase and VSV-G travel in separate post-Golgi transport intermediates, demonstrating directly that multiple routes exist for transport from the Golgi to the basolateral membrane in polarized epithelial cells.
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Glen A
authors.initials: GA
authors.lastname: Farr
authors.forename: Michael
authors.initials: M
authors.lastname: Hull
authors.forename: Ira
authors.initials: I
authors.lastname: Mellman
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caplan
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D004285:Dogs; D011992:Endosomes / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D021381:Protein Transport / Q000502:physiology; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism
chemical_list: D015820:Cadherins; C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D000254:Sodium-Potassium-Exchanging ATPase