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

Bret Wankel, Jiangyong Ouyang, Xuemei Guo, Krassimira Hadjiolova, Jeremy Miller, Yi Liao, Daniel Kai Long Tham, Rok Romih, Leonardo R. Andrade, Iwona Gumper, Jean Pierre Simon, Rakhee Sachdeva, Tanya Tolmachova, Miguel C. Seabra, Mitsunori Fukuda, Nicole Schaeren-Wiemers, Wanjin Hong, David D. Sabatini, Xue Ru Wu, Xiangpeng KongGert Kreibich, Michael J. Rindler, Tung Tien Sun

    Research output: Contribution to journalArticlepeer-review

    13 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)1621-1634
    Number of pages14
    JournalMolecular biology of the cell
    Volume27
    Issue number10
    DOIs
    Publication statusPublished - 2016 May 15

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

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