title: Recycling endosomes of polarized epithelial cells actively sort apical and basolateral cargos into separate subdomains.
abstract: The plasma membranes of epithelial cells plasma membranes contain distinct apical and basolateral domains that are critical for their polarized functions. However, both domains are continuously internalized, with proteins and lipids from each intermixing in supranuclear recycling endosomes (REs). To maintain polarity, REs must faithfully recycle membrane proteins back to the correct plasma membrane domains. We examined sorting within REs and found that apical and basolateral proteins were laterally segregated into subdomains of individual REs. Subdomains were absent in unpolarized cells and developed along with polarization. Subdomains were formed by an active sorting process within REs, which precedes the formation of AP-1B-dependent basolateral transport vesicles. Both the formation of subdomains and the fidelity of basolateral trafficking were dependent on PI3 kinase activity. This suggests that subdomain and transport vesicle formation occur as separate sorting steps and that both processes may contribute to sorting fidelity.
authors.affiliation: Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Thompson
authors.forename: Randy
authors.initials: R
authors.lastname: Nessler
authors.forename: Dolora
authors.initials: D
authors.lastname: Wisco
authors.forename: Eric
authors.initials: E
authors.lastname: Anderson
authors.forename: Bettina
authors.initials: B
authors.lastname: Winckler
authors.forename: David
authors.initials: D
authors.lastname: Sheff
mesh_terms: D033983:Adaptor Protein Complex mu Subunits / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D019062:Cell Adhesion Molecules, Neuron-Glia / Q000378:metabolism; D016764:Cell Polarity; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology*; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D009474:Neurons / Q000166:cytology; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D033983:Adaptor Protein Complex mu Subunits; D019062:Cell Adhesion Molecules, Neuron-Glia; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins