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PMID: 21865156 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Biogenesis of the posterior pole is mediated by the exosome/microvesicle protein-sorting pathway.

The Journal of biological chemistry ·Vol. 286 ·No. 51 ·2011-12-23 ·Pages 44162-44176

Shen B, Fang Y, Wu N, Gould SJ

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.

MeSH Terms
Cell Line, Tumor Cell Membrane/enzymology,metabolism Cell Movement Dictyostelium/metabolism Exosomes/metabolism Green Fluorescent Proteins/metabolism HIV/metabolism HL-60 Cells Humans Jurkat Cells Microscopy, Fluorescence/methods Models, Biological Protein Transport Signal Transduction
Chemicals
Green Fluorescent Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Shen Beiyi
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Fang Yi
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Wu Ning
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
Gould Stephen J
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205. Electronic address: sgould@jhmi.edu.
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
1083-351X
DOI
10.1074/jbc.M111.274803
Email
sgould@jhmi.edu
Published
2011-12-23
Epub
2011-00-24
Pages
44162-44176
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC3243529
Subset
IM
Grants
NIDDK NIH HHS · R01 DK045787 · United States
NIDDK NIH HHS · DK45787 · United States
External Links
PubMed source DOI: 10.1074/jbc.M111.274803 PMC Full Text View journal details
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