Rapid Aquaporin Translocation Regulates Cellular Water Flow

Conner, Matthew T.; Conner, Alex C.; Bland, Charlotte E.; Taylor, Luke H. J.; Brown, James E.; Parri, H. Rheinallt; Bill, Roslyn M.

doi:10.1074/jbc.m111.329219

Cited by 80 publications

(48 citation statements)

References 61 publications

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“…In another study, researchers have demonstrated that ultraviolet radiation (UVB) and H 2 O 2 induced AQP1 down-regulation which was mediated by ERK activation, however, the mechanism was not mentioned in this article [50]. Our results may explain the effect of ERK pathway in translocation and down-regulation of AQP1.There are still distinct findings to identify signaling pathway associated with trafficking of AQP1, such as one recent study reported that AQP1 trafficking was mediated by the tonicity of the cell environment in a specific PKC- and Ca 2+ -dependent manner [16], [17]. Therefore, signaling cascades for translocation of AQP1 still need further examination.…”

Section: Discussionmentioning

confidence: 64%

Aquaporin-1 Translocation and Degradation Mediates the Water Transportation Mechanism of Acetazolamide

Zhang

Gao

et al. 2012

PLoS ONE

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BackgroundDiuretic agents are widely used on the treatment of water retention related diseases, among which acetazolamide (AZA) acts originally as a carbonic anhydrase (CA) inhibitor. Aquaporin-1 (AQP1) being located in renal proximal tubules is required for urine concentration. Previously our lab has reported AZA putatively modulated AQP1. Aim of this study is to testify our hypothesis that regulating AQP1 may mediate diuretic effect of AZA.Methodology/Principal FindingsFor in vivo study, we utilized Sprague Dawley rats, as well as AQP1 knock-out (AQP1−/−) mice to examine urine volume, and human kidney-2 (HK-2) cell line was used for in vitro mechanism study. In our present study we found that AZA decreased CAs activity initially but the activity gradually recovered. Contrarily, diuretic effect was consistently significant. AQP1 protein expression was significantly decreased on day 7 and 14. By utilizing AQP1−/− mice, we found diuretic effect of AZA was cancelled on day 14, while urine volume continuously increased in wild-type mice. Surface plasmon resonance (SPR) results indicated AQP1 was physiologically bound by myosin heavy chain (MHC), immunoprecipitation and immunofluorescence results confirmed this protein interaction. In vitro study results proved AZA facilitated AQP1 translocation onto cell membrane by promoting interaction with MHC, dependent on ERK/ myosin light chain kinase (MLCK) pathway activation. MHC inhibitor BDM and ERK inhibitor U0126 both abolished above effect of AZA. Eventually AZA induced AQP1 ubiquitination, while proteasome inhibitor MG132 reversed AZA's down-regulating effect upon AQP1.Conclusions/SignificanceOur results identified AZA exerted diuretic effect through an innovative mechanism by regulating AQP1 and verified its inhibitory mechanism was via promoting MHC-dependent translocation onto cell membrane and then ubiquitin mediated degradation, implicating a novel mechanism and target for diuretic agent discovering.

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Section: Discussionmentioning

confidence: 64%

Aquaporin-1 Translocation and Degradation Mediates the Water Transportation Mechanism of Acetazolamide

Zhang

Gao

et al. 2012

PLoS ONE

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“…Under normal conditions, approximately 90 % of the filtered volume of water is reabsorbed in the proximal tubule and the thin descending limb of Henle's loop via constitutively expressed AQP1 water channels. Acute regulation of AQP1 is controversial [13]. Water reabsorption in the connecting tubule (CNT) and collecting duct (CD) is under the control of AVP and other signaling molecules and occurs via the apical AQP2 and the basolateral AQP3 and AQP4 water channels.…”

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confidence: 99%

Cell biology of vasopressin-regulated aquaporin-2 trafficking

Moeller

Fenton

2012

Pflugers Arch - Eur J Physiol

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Whole-body water balance is predominantly controlled by the kidneys, which have the ability to concentrate or dilute the urine in the face of altered fluid and solute intake. Regulated water excretion is controlled by various hormones and signaling molecules, with the antidiuretic hormone arginine vasopressin (AVP) playing an essential role, predominantly via its modulatory effects on the function of the water channel aquaporin-2 (AQP2). The clinical conditions, central and nephrogenic diabetes insipidus, emphasize the importance of the AVP-AQP2 axis. In this article, we summarize the most important and recent studies on AVP-regulated trafficking of AQP2, with focus on the cellular components mediating (1) AQP2 vesicle targeting to the principal cell apical plasma membrane, (2) docking and fusion of AQP2-containing vesicles, (3) regulated removal of AQP2 from the plasma membrane, and (4) posttranslational modifications of AQP2 that control several of these processes. Insight into the molecular mechanisms responsible for regulated AQP2 trafficking is proving to be fundamental for development of novel therapies for water balance disorders.

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“…35 Hypotonicity-induced translocation of AQP1 has also been described in HEK293 cells. 36 Another example that illustrates the role of AQPs in cell volume regulation can be seen in sperm, where AQP3 is actively involved in the signaling pathway that activates RVD to protect sperm from excess cell swelling, thereby optimizing postcopulatory sperm behavior. In line with this, the RVD of sperm of AQP3 ¡/¡ mice was inhibited compared to wild-type mice and these knockout mice had lower fertility.…”

Section: Aqps and Cell Volumementioning

confidence: 99%

Role of aquaporins in cell proliferation: What else beyond water permeability?

2016

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In addition to the extensive data demonstrating the importance of mammalian AQPs for the movement of water and some small solutes across the cell membrane, there is now a growing body of evidence indicating the involvement of these proteins in numerous cellular processes seemingly unrelated, at least some of them in a direct way, to their canonical function of water permeation. Here, we have presented a broad range of evidence demonstrating that these proteins have a role in cell proliferation by various different mechanisms, namely, by allowing fast cell volume regulation during cell division; by affecting progression of cell cycle and helping maintain the balance between proliferation and apoptosis, and by crosstalk with other cell membrane proteins or transcription factors that, in turn, modulate progression of the cell cycle or regulate biosynthesis pathways of cell structural components. In the end, however, after discussing all these data that strongly support a role for AQPs in the cell proliferation process, it remains impossible to conclude that all these other functions attributed to AQPs occur completely independently of their water permeability, and there is a need for new experiments designed specifically to address this interesting issue.

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Rapid Aquaporin Translocation Regulates Cellular Water Flow

Cited by 80 publications

References 61 publications

Aquaporin-1 Translocation and Degradation Mediates the Water Transportation Mechanism of Acetazolamide

Aquaporin-1 Translocation and Degradation Mediates the Water Transportation Mechanism of Acetazolamide

Cell biology of vasopressin-regulated aquaporin-2 trafficking

Role of aquaporins in cell proliferation: What else beyond water permeability?

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