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Mol Biol Cell. 2016 May 15;27(10):1621-34. doi: 10.1091/mbc.E15-04-0230. Epub 2016 Mar 23.

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

Author information

1
Department of Cell Biology, New York University School of Medicine, New York, NY10016.
2
Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia.
3
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
4
Molecular and Cellular Medicine, Imperial College, London SW7 2AZ, United Kingdom.
5
Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai 980-8578, Japan.
6
Neurobiology Laboratory, Department of Biomedicine, University Hospital Basel, University of Basel, CH-4031 Basel, Switzerland.
7
Cancer and Developmental Cell Biology Division, Institute of Molecular and Cell Biology, A*STAR, Biopolis, Singapore 138673.
8
Department of Urology, New York University School of Medicine, New York, NY10016.
9
Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY10016.
10
Department of Cell Biology, New York University School of Medicine, New York, NY10016 sunt01@nyumc.org Michael.Rindler@nyumc.org.
11
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.

Abstract

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.

PMID:
27009205
PMCID:
PMC4865319
DOI:
10.1091/mbc.E15-04-0230
[Indexed for MEDLINE]
Free PMC Article

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