A Rab11a-Rab8a-Myo5B network promotes stretch-regulated exocytosis in bladder umbrella cells

Khandelwal, Puneet; Prakasam, H. Sandeep; Clayton, Dennis R.; Ruiz, Wily G.; Gallo, Luciana I.; Roekel, Daniel van; Лукьянов, С. В.; Peränen, Johan; Goldenring, James R.; Apodaca, Gerard

doi:10.1091/mbc.e12-08-0568

Cited by 55 publications

(72 citation statements)

References 79 publications

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“…Reminiscent of the changes in umbrella cell apical surface area (1,15,16,43,53), we observed a significant increase in umbrella cell TJ length in rats whose bladders were allowed to fill to near capacity vs. those in voided or quiescent samples. Strikingly, TJ length decreased by ϳ60% within 5 min of voiding.…”

Section: Discussionmentioning

confidence: 72%

“…This is believed to be mediated in part by profound cell shape changes as they transition from a roughly inverted umbrella parasol shape when voided bladders are examined in cross section, to one that is flat and squamous in filled bladders (2a, 10). Furthermore, during filling, the apical surface area of the umbrella cell is dramatically augmented by the Rab8a-, Rab11a-, Myo5B-, and possibly Rab27b-and MAL-dependent exocytosis of discoidal/fusiformshaped vesicles (6,15,16,53,55), which is reversed by compensatory endocytosis soon after voiding (17). Even so, almost nothing is known about how the TJ adapts to accommodate the structural changes that occur during filling and voiding or how the function of the umbrella cell paracellular barrier is altered during bladder filling and voiding.…”

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confidence: 99%

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Bladder filling and voiding affect umbrella cell tight junction organization and function

Carattino

Prakasam

Ruiz

et al. 2013

American Journal of Physiology-Renal Physiology

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Epithelial cells are continuously exposed to mechanical forces including shear stress and stretch, although the effect these forces have on tight junction (TJ) organization and function are poorly understood. Umbrella cells form the outermost layer of the stratified uroepithelium and undergo large cell shape and surface area changes during the bladder cycle. Here we investigated the effects of bladder filling and voiding on the umbrella cell TJ. We found that bladder filling promoted a significant increase in the length of the TJ ring, which was quickly reversed within 5 min of voiding. Interestingly, when isolated uroepithelial tissue was mounted in Ussing chambers and exposed to physiological stretch, we observed a 10-fold drop in both transepithelial electrical resistance (TER) and the umbrella cell junctional resistance. The effects of stretch on TER were reversible and dependent on the applied force. Furthermore, the integrity of the umbrella cell TJ was maintained in the stretched uroepithelium, as suggested by the limited permeability of biotin, fluorescein, and ruthenium red. Finally, we found that depletion of extracellular Ca(2+) by EGTA completely disrupted the TER of unstretched, but not of stretched uroepithelium. Taken together, our studies indicate that the umbrella cell TJ undergoes major structural and functional reorganization during the bladder cycle. The impact of these changes on bladder function is discussed.

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Section: Discussionmentioning

confidence: 72%

mentioning

confidence: 99%

Bladder filling and voiding affect umbrella cell tight junction organization and function

Carattino

Prakasam

Ruiz

et al. 2013

American Journal of Physiology-Renal Physiology

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“…Rab8-positive vesicles could be dynamically recruited to the plasma membrane by cortical actinmediated transport through interaction with its effectors MyoVa and MyoVb, actin-based motors (Khandelwal et al, 2013;Roland et al, 2007). Rab8 likely allows delivery of microtubule-dependent vesicular cargo to the plasma membrane, acting on the switch between microtubule and actin filament networks through its effector MyoVa, as reported for Rab8-mediated GLUT4 exocytic trafficking in response to insulin (Sun et al, 2014).…”

Section: Discussionmentioning

confidence: 76%

“…Given the recent reports demonstrating involvement of Rab8 in stretch-regulated exocytosis (Khandelwal et al, 2013), it is possible that mechanosensory elements provide the local stimulatory signal triggering Rab8 activity. In this regard, the HCA results presented here show that silencing TRPM7, a stretchactivated cation channel, affects the Rab8-induced cytoskeletal rearrangement profile, a matter that deserves further study.…”

Section: Discussionmentioning

confidence: 99%

A novel high-content analysis tool reveals Rab8-driven cytoskeletal reorganization through Rho GTPases, calpain and MT1-MMP

Bravo‐Cordero

Cordani

Soriano

et al. 2016

Journal of Cell Science

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Rab8 is a small Ras-related GTPase that regulates polarized membrane transport to the plasma membrane. Here, we developed a high-content analysis (HCA) tool to dissect Rab8-mediated actin and focal adhesion reorganization that revealed that Rab8 activation significantly induced Rac1 and Tiam1 to mediate cortical actin polymerization and RhoA-dependent stress fibre disassembly. Rab8 activation increased Rac1 activity, whereas its depletion activated RhoA, which led to reorganization of the actin cytoskeleton. Rab8 was also associated with focal adhesions, promoting their disassembly in a microtubule-dependent manner. This Rab8 effect involved calpain, MT1-MMP (also known as MMP14) and Rho GTPases. Moreover, we demonstrate the role of Rab8 in the cell migration process. Indeed, Rab8 is required for EGF-induced cell polarization and chemotaxis, as well as for the directional persistency of intrinsic cell motility. These data reveal that Rab8 drives cell motility by mechanisms both dependent and independent of Rho GTPases, thereby regulating the establishment of cell polarity, turnover of focal adhesions and actin cytoskeleton rearrangements, thus determining the directionality of cell migration.

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“…Multiple Rabs are associated with secretory granules/vesicles. 32 Rab8 is a small GTPase that controls cell surface structures such as primary cilia, filopodia and neurites by regulating the actin cytoskeleton and the polarized delivery of receptors and vesicles to these specialized membrane domains. 33 Both Rab8 and Rab11 has important roles in regulating cell migration.…”

Section: Discussionmentioning

confidence: 99%

Rab8a/Rab11a regulate intercellular communications between neural cells via tunneling nanotubes

Zhu

Xue

et al. 2016

Cell Death Dis

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Tunneling nanotubes (TNTs) are F-actin-based membrane tubes, and can form between cultured cells and within vital tissues. TNTs mediate intercellular communications that range from electrical signaling to the transfer of organelles. Following peripheral nerve injury, the orchestrated intercellular communications among neural and non-neural cells are required for effective nerve regeneration. It remains unknown whether TNTs exist between neural cells in the peripheral nerve system and how TNTs affect neural regeneration. To address these interesting questions, we investigated the transfer of neurotropic factors, membrane protein, cytoplasmic protein, mitochondria and RNA in functional TNTs formed between cultured Schwann cells (SCs). TNT-like structures were increased not only in cultured SCs after exposure to serum depletion but also in longitudinal sections of proximal sciatic nerve stump harvested after rat peripheral nerve transection. Meanwhile, downregulation of Rab8a or Rab11a in cultured SCs inhibited the formation of functional TNTs and vesicle transfer and led to decrease in cell migration, increase in SCs apoptosis. Likewise, knockdown of Rab8a or Rab11a in primary SCs also suppressed axonal outgrowth from co-cultured dorsal root ganglion (DRG) neurons. Overall, our results suggested that the gene of Rab8a or Rab11a might be involved in the formation of TNTs structures in the peripheral nerve system, while TNTs structures were likely to affect peripheral nerve regeneration through the regulation of neural cell communications.

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A Rab11a-Rab8a-Myo5B network promotes stretch-regulated exocytosis in bladder umbrella cells

Abstract: Rab11a and Rab8 work in conjunction with myosin5B to promote discoidal/fusiform vesicle exocytosis at the apical surface of umbrella cells. It is predicted that similar Rab cascades will be common to other regulated secretory pathways.

Cited by 55 publications

References 79 publications

Bladder filling and voiding affect umbrella cell tight junction organization and function

Bladder filling and voiding affect umbrella cell tight junction organization and function

A novel high-content analysis tool reveals Rab8-driven cytoskeletal reorganization through Rho GTPases, calpain and MT1-MMP

Rab8a/Rab11a regulate intercellular communications between neural cells via tunneling nanotubes

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