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

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

doi:10.1091/mbc.e15-04-0230

Cited by 26 publications

(48 citation statements)

References 81 publications

(131 reference statements)

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“…VAMP3 plays a role in endocytosis in various types of cells (McMahon et al, 1993), but VAMP3 KO mice develop normally. VAMP8 is also expressed in the bladder and is involved in the apical delivery of fusiform vesicles within the umbrella cells (Wankel et al, 2016). VAMP4 KO mice have not been reported.…”

Section: Introductionmentioning

confidence: 98%

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Loss of VAMP5 in mice results in duplication of the ureter and insufficient expansion of the lung

Ikezawa

Tajika

Ueno

et al. 2018

Developmental Dynamics

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Section: Introductionmentioning

confidence: 98%

“…VAMP8 regulates the exocrine systems, and VAMP8 KO mice showed severe defects in the pancreas and kidney (Wang et al, 2004(Wang et al, , 2009. VAMP8 is also expressed in the bladder and is involved in the apical delivery of fusiform vesicles within the umbrella cells (Wankel et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Loss of VAMP5 in mice results in duplication of the ureter and insufficient expansion of the lung

Ikezawa

Tajika

Ueno

et al. 2018

Developmental Dynamics

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“…In umbrella cells, pairs of maturing plaques are assembled within discoidal vesicles, separated by inter-plaque hinge regions that lack the uroplakin complexes. As the bladder fills with urine, the discoidal vesicles are mobilized from the cytosol to add membrane and uroplakins to the lumenal surface of the bladder (54). When the bladder is emptied, excess uroplakin plaques are internalized and degraded through a process referred to as compensatory endocytosis (55).…”

Section: Mechanisms Of Bladder Cell Invasion By Upecmentioning

confidence: 99%

“…This membrane can be derived from various sources, including endosomal compartments, lysosomes, or, in the case of bladder umbrella cells, discoid vesicles. The delivery of membrane to sites of UPEC entry involves small GTP-binding proteins like Rab27b, which can also influence the intracellular trafficking and efflux of uroplakin plaques and UPEC alike (54, 89–91). The silencing of Rab27b expression inhibits UPEC entry into host cells, and internalized UPEC initially localize within Rab27b-positive compartments (82, 89).…”

Section: Mechanisms Of Bladder Cell Invasion By Upecmentioning

confidence: 99%

Invasion of Host Cells and Tissues by Uropathogenic Bacteria

2016

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Within the mammalian urinary tract uropathogenic bacteria face many challenges, including the shearing flow of urine, numerous antibacterial molecules, the bactericidal effects of phagocytes, and a scarcity of nutrients. These problems may be circumvented in part by the ability of uropathogenic Escherichia coli (UPEC) and several other uropathogens to invade the epithelial cells that line the urinary tract. By entering host cells, uropathogens can gain access to additional nutrients and protection from both host defenses and antibiotic treatments. Translocation through host cells can facilitate bacterial dissemination within the urinary tract, while the establishment of stable intracellular bacterial populations may create reservoirs for relapsing and chronic urinary tract infections (UTIs). Here we review the mechanisms and consequences of host cell invasion by uropathogenic bacteria, with consideration of the defenses that are brought to bear against facultative intracellular pathogens within the urinary tract. The relevance of host cell invasion to the pathogenesis of UTIs in human patients is also assessed, along with some of the emerging treatment options that build upon our growing understanding of the infectious life cycle of UPEC and other uropathogenic bacteria.

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“…Superficial urothelial cells contain unique cytoplasmic organelles including fusiform vesicles, which deliver preassembled UPK (uroplakin) proteins to the apical cell surface during bladder filling. Recent studies have demonstrated that specific small RAB GTPases (RAB27B and RAB11A) are highly enriched in superficial urothelial cells and are important for vesicle trafficking, UPK recycling [23][24][25][26][27][28], and exosome-mediated expulsion of intracellular UPEC [29][30][31]. Interestingly, network mapping of autophagy pathways has identified a Golgi-resident small GTPase, RAB33B, which interacts directly with ATG16L1 and thereby modulates autophagosome formation [32].…”

Section: Introductionmentioning

confidence: 99%

A non-canonical autophagy-dependent role of the ATG16L1^T300A variant in urothelial vesicular trafficking and uropathogenic Escherichia coli persistence

et al. 2018

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50% of Caucasians carry a Thr300Ala variant (T300A) in the protein encoded by the macroautophagy/ autophagy gene ATG16L1. Here, we show that the T300A variant confers protection against urinary tract infections (UTIs), the most common infectious disease in women. Using knockin mice carrying the human T300A variant, we show that the variant limits the UTI-causing bacteria, uropathogenic Escherichia coli (UPEC), from establishing persistent intracellular reservoirs, which can seed UTI recurrence. This phenotype is recapitulated in mice lacking Atg16l1 or Atg7 exclusively in the urothelium. We further show that mice with the T300A variant exhibit urothelial cellular abnormalities, including vesicular congestion and aberrant accumulation of UPK (uroplakin) proteins. Importantly, presence of the T300A variant in humans is associated with similar urothelial architectural abnormalities, indicating an evolutionarily conserved impact. Mechanistically, we show that the reduced bacterial persistence is independent of basal autophagic flux or proinflammatory cytokine responses and does not involve Atg14 or Epg5. However, the T300A variant is associated with increased expression of the small GTPase Rab33b; RAB33B interacts with ATG16L1, as well as other secretory RABs, RAB27B and RAB11A, important for UPEC exocytosis from the urothelium. Finally, inhibition of secretory RABs in bladder epithelial cells increases intracellular UPEC load. Together, our results reveal that UPEC selectively utilize genes important for autophagosome formation to persist in the urothelium, and that the presence of the T300A variant in ATG16L1 is associated with changes in urothelial vesicle trafficking, which disrupts the ability of UPEC to persist, thereby limiting the risk of recurrent UTIs.Abbreviations: 3-PEHPC: 3-pyridinyl ethylidene hydroxyl phosphonocarboxylate; ATG: autophagy; ATG16L1: autophagy related 16 like 1; BECs: bladder epithelial cells; dpi: days post infection; hpi: hours post infection; IF: immunofluorescence; IL1B: interleukin 1 beta; IL6: interleukin 6; MAP1LC3B/ LC3B: microtubule-associated protein 1 light chain 3 beta; MVB: multivesicular bodies; T300A: Thr300Ala; TNF: tumor necrosis factor; QIR(s): quiescent intracellular reservoir(s); siRNA: short interfering RNA; UPEC: uropathogenic Escherichia coli; UTI(s): urinary tract infection(s); TEM: transmission electron microscopy; WT: wild type ARTICLE HISTORY

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

Cited by 26 publications

References 81 publications

Loss of VAMP5 in mice results in duplication of the ureter and insufficient expansion of the lung

Loss of VAMP5 in mice results in duplication of the ureter and insufficient expansion of the lung

Invasion of Host Cells and Tissues by Uropathogenic Bacteria

A non-canonical autophagy-dependent role of the ATG16L1^T300A variant in urothelial vesicular trafficking and uropathogenic Escherichia coli persistence

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

Cited by 26 publications

References 81 publications

Loss of VAMP5 in mice results in duplication of the ureter and insufficient expansion of the lung

Loss of VAMP5 in mice results in duplication of the ureter and insufficient expansion of the lung

Invasion of Host Cells and Tissues by Uropathogenic Bacteria

A non-canonical autophagy-dependent role of the ATG16L1T300A variant in urothelial vesicular trafficking and uropathogenic Escherichia coli persistence

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A non-canonical autophagy-dependent role of the ATG16L1^T300A variant in urothelial vesicular trafficking and uropathogenic Escherichia coli persistence