title: Biogenesis of the posterior pole is mediated by the exosome/microvesicle protein-sorting pathway.
abstract: Biogenesis of the posterior pole is critical to directed cell migration and other polarity-dependent processes. We show here that proteins are targeted to the posterior pole on the basis of higher order oligomerization and plasma membrane binding, the same elements that target proteins to exosomes/microvesicles (EMVs), HIV, and other retrovirus particles. We also demonstrate that the polarization of the EMV protein-sorting pathway can occur in morphologically non-polarized cells, defines the site of uropod formation, is induced by increased expression of EMV cargo proteins, and is evolutionarily conserved between humans and the protozoan Dictyostelium discoideum. Based on these results, we propose a mechanism of posterior pole biogenesis in which elevated levels of EMV cargoes (i) polarize the EMV protein-sorting pathway, (ii) generate a nascent posterior pole, and (iii) prime cells for signal-induced biogenesis of a uropod. This model also offers a mechanistic explanation for the polarized budding of EMVs and retroviruses, including HIV.
authors.affiliation: Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Beiyi
authors.initials: B
authors.lastname: Shen
authors.affiliation: Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: Ning
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205. Electronic address: sgould@jhmi.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gould
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism*; D002465:Cell Movement; D004023:Dictyostelium / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006678:HIV / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D019169:Jurkat Cells; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D021381:Protein Transport; D015398:Signal Transduction
chemical_list: D049452:Green Fluorescent Proteins