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Cited by 13Lipid Membrane Structure and BehaviorAdvanced Electron Microscopy Techniques and ApplicationsSkin and Cellular Biology Research

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Cryo-EM elucidates the uroplakin complex structure within liquid-crystalline lipids in the porcine urothelial membrane

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Yanagisawa, Haruaki, Kita, Yoshihiro, Oda, Toshiyuki, Kikkawa, Masahide·2023·Communications Biology
DOI 10.1038/s42003-023-05393-xPMC PMC10560298

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Abstract

The urothelium, a distinct epithelial tissue lining the urinary tract, serves as an essential component in preserving urinary tract integrity and thwarting infections. The asymmetric unit membrane (AUM), primarily composed of the uroplakin complex, constitutes a critical permeability barrier in fulfilling this role. However, the molecular architectures of both the AUM and the uroplakin complex have remained enigmatic due to the paucity of high-resolution structural data. In this study, we utilized cryo-electron microscopy to elucidate the three-dimensional structure of the uroplakin complex within the porcine AUM. While the global resolution achieved was 3.5 Å, we acknowledge that due to orientation bias, the resolution in the vertical direction was determined to be 6.3 Å. Our findings unveiled that the uroplakin complexes are situated within hexagonally arranged crystalline lipid membrane domains, rich in hexosylceramides. Moreover, our research rectifies a misconception in a previous model by confirming the existence of a domain initially believed to be absent, and pinpointing the accurate location of a crucial Escherichia coli binding site implicated in urinary tract infections. These discoveries offer valuable insights into the molecular underpinnings governing the permeability barrier function of the urothelium and the orchestrated lipid phase formation within the plasma membrane.

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Metadata

Authors
Yanagisawa, H., Kita, Y., Oda, T., & Kikkawa, M.
Affiliations
  • The University of Tokyo (JP)
  • University of Yamanashi (JP)
Corresponding author
  • Oda, Toshiyuki
  • Kikkawa, Masahide
ORCID
Venue
Communications Biology
Publisher
Springer Science and Business Media LLC
Published
2023-10-07
Volume
6
Issue
1
Pages
1018-1018
ISSN
2399-3642 (ISSN-L)
DOI
10.1038/s42003-023-05393-x
PMC
PMC10560298
OpenAlex
W4387425865
Cited by
13
References
2
Citations by year
2026: 2 · 2025: 9 · 2024: 2
FWCI
1.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Communications Biology (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • MEXT | Japan Society for the Promotion of Science (JP21H02654, JP22H05538, JP21H05248)
  • Takeda Science Foundation
  • Daiichi Sankyo Foundation of Life Science
  • Naito Foundation
  • Japan Agency for Medical Research and Development (JP22ama121002, JP23ama121002)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
Keywords
urothelium, hexosylceramide, urinary tract infection, permeability barrier, membrane protein structure

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