Distinct Apical and Basolateral Membrane Requirements for Stretch-induced Membrane Traffic at the Apical Surface of Bladder Umbrella Cells

Yu, Weiqun; Khandelwal, Puneet; Apodaca, Gerard

doi:10.1091/mbc.e08-04-0439

Cited by 57 publications

(140 citation statements)

References 48 publications

(86 reference statements)

Supporting

Mentioning

130

Contrasting

Order By: Relevance

“…Once considered an inert barrier, the urothelium is now proposed to be a mechanosensor (4,61). Our observation that 22 TRP channels may be expressed in this tissue provides additional support for this hypothesis.…”

Section: Discussionsupporting

confidence: 53%

“…In addition to its role as a barrier, the umbrella cell and subjacent intermediate and basal cell layers also have a sensory function and in response to various physical and chemical stimuli can release neurotransmitters (such as ATP and nitric oxide), which then communicate the state of the tissue's external environment to afferent neurons (3,4). The response to mechanical and other stimuli may depend, in part, on the function of umbrella cell-associated ion channels, which when opened or closed can alter membrane potential (32,61). Possible sensory channels include the epithelial sodium channel (ENaC), various mechanically sensitive potassium channels (33,61), and nonselective cation channels whose identity are unknown but may play an important role in mechanotransduction (55,61).…”

mentioning

confidence: 99%

“…The response to mechanical and other stimuli may depend, in part, on the function of umbrella cell-associated ion channels, which when opened or closed can alter membrane potential (32,61). Possible sensory channels include the epithelial sodium channel (ENaC), various mechanically sensitive potassium channels (33,61), and nonselective cation channels whose identity are unknown but may play an important role in mechanotransduction (55,61). Other potential ion channels with sensory activity expressed by the umbrella cells and the other urothelial cell layers include the purinergic P2X family channels and members of the transient receptor potential (TRP) family of channels.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Expression and distribution of transient receptor potential (TRP) channels in bladder epithelium

Hill

Apodaca

et al. 2011

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

The urothelium is proposed to be a sensory tissue that responds to mechanical stress by undergoing dynamic membrane trafficking and neurotransmitter release; however, the molecular basis of this function is poorly understood. Transient receptor potential (TRP) channels are ideal candidates to fulfill such a role as they can sense changes in temperature, osmolarity, and mechanical stimuli, and several are reported to be expressed in the bladder epithelium. However, their complete expression profile is unknown and their cellular localization is largely undefined. We analyzed expression of all 33 TRP family members in mouse bladder and urothelium by RT-PCR and found 22 specifically expressed in the urothelium. Of the latter, 10 were chosen for closer investigation based on their known mechanosensory or membrane trafficking functions in other cell types. Western blots confirmed urothelial expression of TRPC1, TRPC4, TRPV1, TRPV2, TRPV4, TRPM4, TRPM7, TRPML1, and polycystins 1 and 2 (PKD1 and PKD2) proteins. We further defined the cellular and subcellular localization of all 10 TRP channels. TRPV2 and TRPM4 were prominently localized to the umbrella cell apical membrane, while TRPC4 and TRPV4 were identified on their abluminal surfaces. TRPC1, TRPM7, and TRPML1 were localized to the cytoplasm, while PKD1 and PKD2 were expressed on the apical and basolateral membranes of umbrella cells as well as in the cytoplasm. The cellular location of TRPV1 in the bladder has been debated, but colocalization with neuronal marker calcitonin gene-related peptide indicated clearly that it is present on afferent neurons that extend into the urothelium, but may not be expressed by the urothelium itself. These findings are consistent with the hypothesis that the urothelium acts as a sentinel and by expressing multiple TRP channels it is likely it can detect and presumably respond to a diversity of external stimuli and suggest that it plays an important role in urothelial signal transduction.

show abstract

Section: Discussionsupporting

confidence: 53%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Expression and distribution of transient receptor potential (TRP) channels in bladder epithelium

Hill

Apodaca

et al. 2011

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Since there are contradicting results regarding endocytosis in urothelial cells, 3,19,37,38 we used the AuNPs to follow internalization into superficial urothelial cells of normal and neoplastic urothelium.…”

Section: Discussionmentioning

confidence: 99%

Gold nanoparticles as physiological markers of urine internalization into urothelial cells in vivo

Hudoklin¹,

Zupančič²,

Makovec³

et al. 2013

IJN

View full text Add to dashboard Cite

Background: Urothelial bladder is the reservoir of urine and the urothelium minimizes the exchange of urine constituents with this tissue. Our aim was to test 1.9 nm biocompatible gold nanoparticles as a novel marker of internalization into the urothelial cells under physiological conditions in vivo. Methods: We compared normal and neoplastic mice urothelium. Neoplastic lesions were induced by 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in drinking water for 10 weeks. Nanoparticles, intravenously injected into normal and BBN-treated mice, were filtered through the kidneys and became constituents of the urine within 90 minutes after injection. Results: Gold nanoparticles were densely accumulated in the urine, while their internalization into urothelial cells depended on the cell differentiation stage. In the terminally differentiated superficial urothelial cells of normal animals, nanoparticles were occasionally found in the endosomes, but not in the fusiform vesicles. Regions of exfoliated cells were occasionally found in the normal urothelium. Superficial urothelial cells located next to exfoliated regions contained gold nanoparticles in the endosomes and in the cytosol beneath the apical plasma membrane. The urothelium of BBN-treated animals developed flat hyperplasia with moderate dysplasia. The superficial cells of BBN-treated animals were partially differentiated as demonstrated by the lack of fusiform vesicles. These cells contained the gold nanoparticles distributed in the endosomes and throughout their cytosol. Conclusion: Gold nanoparticles are a valuable marker to study urine internalization into urothelial cells in vivo. Moreover, they can be used as a sensitive marker of differentiation and functionality of urothelial cells.

show abstract

“…[29][30][31][32] Mechanical stimuli are potent mitogens for mechanosensitive cells such as fibroblasts and osteoblasts. 33,34 Increasing evidence suggests that neural tissues are also directly mechanically sensitive.…”

Section: Discussionmentioning

confidence: 99%

Biophysical stimulation induces demyelination via an integrin‐dependent mechanism

Lin

Frieboes

Forootan

et al. 2012

Annals of Neurology

View full text Add to dashboard Cite

Objective: Chronic nerve compression (CNC) injuries occur when peripheral nerves are subjected to sustained mechanical forces, with increasing evidence implicating Schwann cells as key mediators. Integrins, a family of transmembrane adhesion molecules that are capable of intracellular signaling, have been implicated in a variety of biological processes such as myelination and nerve regeneration. In this study, we seek to define the physical stimuli mediating demyelination and to determine whether integrin plays a role in the demyelinating response. Methods: We used a previously described in vitro model of CNC injury where myelinating neuron-Schwann cell cocultures were subjected to independent manipulations of hydrostatic pressure, hypoxia, and glucose deprivation in a custom bioreactor. We assessed whether demyelination increased in response to applied manipulation and determined whether integrin-associated signaling cascades are upregulated. Results: Biophysical stimulation of neural tissue induced demyelination and Schwann cell proliferation without neuronal or glial cytotoxicity or apoptosis. Although glucose deprivation and hypoxia independently had minor effects on myelin stability, together they potentiated the demyelinating effects of hydrostatic compression, and in combination, significantly destabilized myelin. Biophysical stimuli transiently increased phosphorylation of the integrin-associated tyrosine kinase Src within Schwann cells. Silencing this integrin signaling cascade blocked Src activation and prevented pressure-induced demyelination. Colocalization analysis indicated that Src is localized within Schwann cells. Interpretation: These results indicate that myelin is sensitive to CNC injury and support the novel concept that myelinating cocultures respond directly to mechanical loading via activating an integrin signaling cascade.

show abstract

Distinct Apical and Basolateral Membrane Requirements for Stretch-induced Membrane Traffic at the Apical Surface of Bladder Umbrella Cells

Cited by 57 publications

References 48 publications

Expression and distribution of transient receptor potential (TRP) channels in bladder epithelium

Expression and distribution of transient receptor potential (TRP) channels in bladder epithelium

Gold nanoparticles as physiological markers of urine internalization into urothelial cells in vivo

Biophysical stimulation induces demyelination via an integrin‐dependent mechanism

Contact Info

Product

Resources

About