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

Wankel, Bret and Ouyang, Jiangyong and Guo, Xuemei and Hadjiolova, Krassimira and Miller, Jeremy and Liao, Yi and Tham, Daniel Kai Long and Romih, Rok and Andrade, Leonardo R. and Gumper, Iwona and Simon, Jean-Pierre and Sachdeva, Rakhee and Tolmachova, Tanya and Seabra, Miguel C. and Fukuda, Mitsunori and Schaeren-Wiemers, Nicole and Hong, Wan Jin and Sabatini, David D. and Wu, Xue-Ru and Kong, Xiangpeng and Kreibich, Gert and Rindler, Michael J. and Sun, Tung-Tien. (2016) Sequential and compartmentalized action of Rabs, SNAREs, and MAL in the apical delivery of fusiform vesicles in urothelial umbrella cells. Molecular biology of the cell, 27 (10). pp. 1621-1634.

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Official URL: https://edoc.unibas.ch/62088/

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Neurobiology (Schaeren-Wiemers)
UniBasel Contributors:Schaeren-Wiemers, Nicole
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:31 May 2020 17:34
Deposited On:31 May 2020 17:34

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