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Sequential and compartmentalized action of Rabs, SNAREs, and MAL in the apical delivery of fusiform vesicles in urothelial umbrella cells.
Journal article

Sequential and compartmentalized action of Rabs, SNAREs, and MAL in the apical delivery of fusiform vesicles in urothelial umbrella cells.

  • Wankel B Department of Cell Biology, New York University School of Medicine, New York, NY10016.
  • Ouyang J Department of Cell Biology, New York University School of Medicine, New York, NY10016.
  • Guo X Department of Cell Biology, New York University School of Medicine, New York, NY10016.
  • Hadjiolova K Department of Cell Biology, New York University School of Medicine, New York, NY10016.
  • Miller J Department of Cell Biology, New York University School of Medicine, New York, NY10016.
  • Liao Y Department of Cell Biology, New York University School of Medicine, New York, NY10016.
  • Tham DK Department of Cell Biology, New York University School of Medicine, New York, NY10016.
  • Romih R Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
  • Andrade LR Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
  • Gumper I Department of Cell Biology, New York University School of Medicine, New York, NY10016.
  • Simon JP Department of Cell Biology, New York University School of Medicine, New York, NY10016.
  • Sachdeva R Department of Cell Biology, New York University School of Medicine, New York, NY10016.
  • Tolmachova T Molecular and Cellular Medicine, Imperial College, London SW7 2AZ, United Kingdom.
  • Seabra MC Molecular and Cellular Medicine, Imperial College, London SW7 2AZ, United Kingdom.
  • Fukuda M Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai 980-8578, Japan.
  • Schaeren-Wiemers N Neurobiology Laboratory, Department of Biomedicine, University Hospital Basel, University of Basel, CH-4031 Basel, Switzerland.
  • Hong WJ Cancer and Developmental Cell Biology Division, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
  • Sabatini DD Department of Cell Biology, New York University School of Medicine, New York, NY10016.
  • Wu XR Department of Urology, New York University School of Medicine, New York, NY10016.
  • Kong X Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY10016.
  • Kreibich G Department of Cell Biology, New York University School of Medicine, New York, NY10016.
  • Rindler MJ Department of Cell Biology, New York University School of Medicine, New York, NY10016 sunt01@nyumc.org Michael.Rindler@nyumc.org.
  • Sun TT Department of Cell Biology, New York University School of Medicine, New York, NY10016 Department of Urology, New York University School of Medicine, New York, NY10016 Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY10016 Department of Dermatology, New York University School of Medicine, New York, NY10016 sunt01@nyumc.org Michael.Rindler@nyumc.org.
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  • 2016-03-25
Published in:
  • Molecular biology of the cell. - 2016
Animals
Cell Differentiation
Cell Membrane
Cells, Cultured
Epithelial Cells
Keratin-20
MARVEL Domain-Containing Proteins
Mice
Mice, Inbred C57BL
Muscle, Smooth
Protein Transport
SNARE Proteins
Uroplakins
Urothelium
rab GTP-Binding Proteins
English Uroplakins (UPs) are major differentiation products of urothelial umbrella cells and play important roles in forming the permeability barrier and in the expansion/stabilization of the apical membrane. Further, UPIa serves as a uropathogenic Escherichia coli receptor. Although it is understood that UPs are delivered to the apical membrane via fusiform vesicles (FVs), the mechanisms that regulate this exocytic pathway remain poorly understood. Immunomicroscopy of normal and mutant mouse urothelia show that the UP-delivering FVs contained Rab8/11 and Rab27b/Slac2-a, which mediate apical transport along actin filaments. Subsequently a Rab27b/Slp2-a complex mediated FV-membrane anchorage before SNARE-mediated and MAL-facilitated apical fusion. We also show that keratin 20 (K20), which forms a chicken-wire network ∼200 nm below the apical membrane and has hole sizes allowing FV passage, defines a subapical compartment containing FVs primed and strategically located for fusion. Finally, we show that Rab8/11 and Rab27b function in the same pathway, Rab27b knockout leads to uroplakin and Slp2-a destabilization, and Rab27b works upstream from MAL. These data support a unifying model in which UP cargoes are targeted for apical insertion via sequential interactions with Rabs and their effectors, SNAREs and MAL, and in which K20 plays a key role in regulating vesicular trafficking.
Language
  • English
Open access status
hybrid
Identifiers
Persistent URL
https://sonar.ch/global/documents/232409
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