A novel human aquaporin-4 splice variant exhibits a dominant-negative activity: a new mechanism to regulate water permeability

Bellis, Manuela De; Pisani, Francesco; Mola, Maria Grazia; Basco, Davide; Catalano, F. A.; Nicchia, Grazia Paola; Svelto, María; Frigeri, Antonio

doi:10.1091/mbc.e13-06-0331

Cited by 37 publications

(54 citation statements)

References 35 publications

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“…It has been invariably measured around 1.5–5 h regardless of the cell type, leading to the rapid turnover of gap junction plaques [24–26]. In contrast, the half-life of Aqp4 would be >8 h [27] and >24 h for Glt1 (Slc1a2) [28]. We compared the level of these proteins on western blot of proteins extracted from brain vessel-associated endfeet treated or untreated with CHX for 6 h (Figure 5b).…”

Section: Resultsmentioning

confidence: 99%

Translation in astrocyte distal processes sets molecular heterogeneity at the gliovascular interface

et al. 2017

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Astrocytes send out long processes that are terminated by endfeet at the vascular surface and regulate vascular functions as well as homeostasis at the vascular interface. To date, the astroglial mechanisms underlying these functions have been poorly addressed. Here we demonstrate that a subset of messenger RNAs is distributed in astrocyte endfeet. We identified, among this transcriptome, a pool of messenger RNAs bound to ribosomes, the endfeetome, that primarily encodes for secreted and membrane proteins. We detected nascent protein synthesis in astrocyte endfeet. Finally, we determined the presence of smooth and rough endoplasmic reticulum and the Golgi apparatus in astrocyte perivascular processes and endfeet, suggesting for local maturation of membrane and secreted proteins. These results demonstrate for the first time that protein synthesis occurs in astrocyte perivascular distal processes that may sustain their structural and functional polarization at the vascular interface.

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Section: Resultsmentioning

confidence: 99%

Translation in astrocyte distal processes sets molecular heterogeneity at the gliovascular interface

et al. 2017

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“…AQP4 exists in two major isoforms (although there is emerging evidence of further isoforms [184]). These are the long (323 amino acids) M1 isoform and the shorter (301 amino acids) M23 isoform, named for the position of the N-terminal methionine.…”

Section: Aqp4mentioning

confidence: 99%

Beyond water homeostasis: Diverse functional roles of mammalian aquaporins

Kitchen

Day

Salman

et al. 2015

Biochimica et Biophysica Acta (BBA) - General Subjects

128

115

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BACKGROUND: Aquaporin (AQP) water channels are best known as passive transporters of water that are vital for water homeostasis. SCOPE OF REVIEW:AQP knockout studies in whole animals and cultured cells, along with naturally occurring human mutations suggest that the transport of neutral solutes through AQPs has important physiological roles. Emerging biophysical evidence suggests that AQPs may also facilitate gas (CO2) and cation transport. AQPs may be involved in cell signalling for volume regulation and controlling the subcellular localization of other proteins by forming macromolecular complexes. This review examines the evidence for these diverse functions of AQPs as well their physiological relevance. MAJOR CONCLUSIONS:As well as being crucial for water homeostasis, AQPs are involved in physiologically important transport of molecules other than water, regulation of surface expression of other membrane proteins, cell adhesion, and signalling in cell volume regulation. GENERAL SIGNIFICANCE:Elucidating the full range of functional roles of AQPs beyond the passive conduction of water will improve our understanding of mammalian physiology in health and disease. The functional variety of AQPs makes them an exciting drug target and could provide routes to a range of novel therapies.3

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“…The ER-localized E3 ubiquitin ligase Rma1H1 is induced by various abiotic stresses, and it inhibits the trafficking of PIP2;1 to the plasma membrane and targets the aquaporin for proteasomal degradation as a response to dehydration (Lee et al, 2009). AQPD4 is an alternative spliced variant of the human aquaporin AQP4 lacking exon 4 that exhibits no water activity and is retained in the ER (De Bellis et al, 2014). When AQPD4 is expressed in the presence of functional AQP4, the surface expression of the full-length protein is reduced, and water activity at the plasma membrane is diminished in comparison to cells expressing AQP4 alone.…”

Section: Tspo Interacts With and Acts As A Transient Regulator Of Pip2;7mentioning

confidence: 99%

“…When AQPD4 is expressed in the presence of functional AQP4, the surface expression of the full-length protein is reduced, and water activity at the plasma membrane is diminished in comparison to cells expressing AQP4 alone. AQPD4 forms dimers with AQP4 in the ER and targets the complex for proteasomal degradation, therefore acting as a dominant-negative regulator (De Bellis et al, 2014). It seems that, at least for some plasma membrane aquaporins, protein-protein interaction and downregulation of the complex is a common regulatory mechanism although the regulator and pathway may vary.…”

Section: Tspo Interacts With and Acts As A Transient Regulator Of Pip2;7mentioning

confidence: 99%

The Arabidopsis Abiotic Stress-Induced TSPO-Related Protein Reduces Cell-Surface Expression of the Aquaporin PIP2;7 through Protein-Protein Interactions and Autophagic Degradation

et al. 2014

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The Arabidopsis thaliana multi-stress regulator TSPO is transiently induced by abiotic stresses. The final destination of this polytopic membrane protein is the Golgi apparatus, where its accumulation is strictly regulated, and TSPO is downregulated through a selective autophagic pathway. TSPO-related proteins regulate the physiology of the cell by generating functional protein complexes. A split-ubiquitin screen for potential TSPO interacting partners uncovered a plasma membrane aquaporin, PIP2;7. Pull-down assays and fluorescence imaging approaches revealed that TSPO physically interacts with PIP2;7 at the endoplasmic reticulum and Golgi membranes in planta. Intriguingly, constitutive expression of fluorescently tagged PIP2;7 in TSPO-overexpressing transgenic lines resulted in patchy distribution of the fluorescence, reminiscent of the pattern of constitutively expressed yellow fluorescent protein-TSPO in Arabidopsis. Mutational stabilization of TSPO or pharmacological inhibition of the autophagic pathway affected concomitantly the detected levels of PIP2;7, suggesting that the complex containing both proteins is degraded through the autophagic pathway. Coexpression of TSPO and PIP2;7 resulted in decreased levels of PIP2;7 in the plasma membrane and abolished the membrane water permeability mediated by transgenic PIP2;7. Taken together, these data support a physiological role for TSPO in regulating the cell-surface expression of PIP2;7 during abiotic stress conditions through protein-protein interaction and demonstrate an aquaporin regulatory mechanism involving TSPO. INTRODUCTIONEnvironmental stresses such as drought, salinity, or cold are common limiting factors for plant growth and development. These stresses impose osmotic and oxidative stresses at the cellular level, and a critical function of the phytohormone abscisic acid (ABA) is to mediate the plant response to these insults during vegetative growth (Finkelstein et al., 2002;Nambara and Marion-Poll, 2005;Yamaguchi-Shinozaki and Shinozaki, 2006). The increase in active ABA levels in plant cells during water-related stress regulates the expression of ABA-responsive genes by interacting with cytosolic and/or organelle-bound receptors and downstream effectors modulating the activity of defined transcriptional regulators (Fujii and Zhu, 2009;Ma et al., 2009;Park et al., 2009;Wu et al., 2009;Shang et al., 2010). It is thought that up to 10% of the Arabidopsis thaliana transcriptome is responsive to ABA signaling . Extensive studies of stress and ABA-induced gene expression during vegetative growth revealed two waves of response: an early transient response peaking at ;3 h and a late sustained response from 10 h onward (reviewed in Finkelstein, 2013). Characteristically, the so-called "early" genes encode regulatory proteins, such as transcription factors, protein kinases, and phosphatases, and a set of proteins of unknown function Fujita et al., 2006). The "late" genes are presumed to contribute to plant adaptation to the stress and encode proteins such as ...

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A novel human aquaporin-4 splice variant exhibits a dominant-negative activity: a new mechanism to regulate water permeability

Cited by 37 publications

References 35 publications

Translation in astrocyte distal processes sets molecular heterogeneity at the gliovascular interface

Translation in astrocyte distal processes sets molecular heterogeneity at the gliovascular interface

Beyond water homeostasis: Diverse functional roles of mammalian aquaporins

The Arabidopsis Abiotic Stress-Induced TSPO-Related Protein Reduces Cell-Surface Expression of the Aquaporin PIP2;7 through Protein-Protein Interactions and Autophagic Degradation

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