AQP2 trafficking in health and diseases: an updated overview

Centrone, Mariangela; Ranieri, Marianna; Mise, Annarita Di; D’Agostino, Mariagrazia; Venneri, Maria; Ferrulli, Angela; Valenti, Giovanna; Tamma, Grazia

doi:10.1016/j.biocel.2022.106261

Cited by 12 publications

(10 citation statements)

References 175 publications

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“…Microtubules have been shown to be an important component of AQP2 trafficking. They have been associated with both the internalisation of the water channel as well as targeting to the cell surface (reviewed in (Centrone et al., 2022)).…”

Section: Discussionmentioning

confidence: 99%

“…The translocation mechanisms of the 13 human AQPs have been described to varying degrees (Markou et al., 2022). The most well understood is that of AQP2, which is expressed in the kidney collecting duct and is triggered by vasopressin (Centrone et al., 2022). The trafficking mechanism of AQP4 has been shown to be calmodulin (CaM) and phosphorylation dependent (Ishida et al., 2022; Kitchen, Day, Salman, et al., 2015; Kitchen, Day, Taylor, et al., 2015).…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms of aquaporin‐4 vesicular trafficking in mammalian cells

Markou,

Kitchen,

Aldabbagh

et al. 2023

Journal of Neurochemistry

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The aquaporin‐4 (AQP4) water channel is abundantly expressed in the glial cells of the central nervous system and facilitates brain swelling following diverse insults, such as traumatic injury or stroke. Lack of specific and therapeutic AQP4 inhibitors highlights the need to explore alternative routes to control the water permeability of glial cell membranes. The cell surface abundance of AQP4 in mammalian cells fluctuates rapidly in response to changes in oxygen levels and tonicity, suggesting a role for vesicular trafficking in its translocation to and from the cell surface. However, the molecular mechanisms of AQP4 trafficking are not fully elucidated. In this work, early and recycling endosomes were investigated as likely candidates of rapid AQP4 translocation together with changes in cytoskeletal dynamics. In transiently transfected HEK293 cells a significant amount of AQP‐eGFP colocalised with mCherry‐Rab5‐positive early endosomes and mCherry‐Rab11‐positive recycling endosomes. When exposed to hypotonic conditions, AQP4‐eGFP rapidly translocated from intracellular vesicles to the cell surface. Co‐expression of dominant negative forms of the mCherry‐Rab5 and ‐Rab11 with AQP4‐eGFP prevented hypotonicity‐induced AQP4‐eGFP trafficking and led to concentration at the cell surface or intracellular vesicles respectively. Use of endocytosis inhibiting drugs indicated that AQP4 internalisation was dynamin‐dependent. Cytoskeleton dynamics‐modifying drugs also affected AQP4 translocation to and from the cell surface. AQP4 trafficking mechanisms were validated in primary human astrocytes, which express high levels of endogenous AQP4. The results highlight the role of early and recycling endosomes and cytoskeletal dynamics in AQP4 translocation in response to hypotonic and hypoxic stress and suggest continuous cycling of AQP4 between intracellular vesicles and the cell surface under physiological conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mechanisms of aquaporin‐4 vesicular trafficking in mammalian cells

Markou,

Kitchen,

Aldabbagh

et al. 2023

Journal of Neurochemistry

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“…AQP2, a channel that is selective only for water molecules and impermeable to ions or other small molecules, is an aquaporin regulated by arginine vasopressin [2,35]. Normal functioning of AQP2 depends on multiple posttranslational modifications, and aberrant arginine vasopressin signaling and altered AQP2 expression or transport can lead to diseases characterized by dysregulation of mechanisms controlling water homeostasis [36]. Impairment of AQP2 results in various water balance disorders, including disorders associated with polyuria (urinary tract obstruction, hypokalemia, inflammation, and lithium intoxication), dilutive hyponatremia (improper antidiuretic syndrome, congestive heart failure, cirrhosis syndrome), and Ménière's Disease [37,38].…”

Section: Aqp2mentioning

confidence: 99%

Aquaporins and Neuropathic Pain

Wang¹,

Xu²,

Xu³

et al. 2023

Front. Biosci. (Landmark Ed)

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Neuropathic pain is a chronic secondary pain condition resulting from lesions or diseases of the peripheral or central nervous system (CNS). Neuropathic pain is closely related to edema, inflammation, increased neuronal excitability, and central sensitization caused by glutamate accumulation. Aquaporins (AQPs), mainly responsible for the transport and clearance of water and solute, play important roles in developing CNS diseases, especially neuropathic pain. This review focuses on the interaction of AQPs with neuropathic pain, and the potential of AQPs, especially aquaporins 4, as therapeutic targets.

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“…The vasopressin-dependent activation of cyclic adenosine monophosphate-dependent kinase A (protein kinase A) leads to the phosphorylation of AQP2 at serine 256 (S256), which is considered a priming event for downstream phosphorylation at S269 and S264. Vasopressin stimulation also results in the significant dephosphorylation of AQP2 at S261 [24][25][26]. There are a trio of putative potential ubiquitination sites (cytosolic lysine residues) within the C-terminal domain of AQP2 (K228, K238, and K270).…”

Section: Aquaporins In the Kidneymentioning

confidence: 99%

Autophagy and regulation of aquaporins in the kidneys

Xiang-dong

Kong

Kwon

et al. 2023

Kidney Res Clin Pract

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Aquaporins (AQPs) are water channel proteins that facilitate the transport of water molecules across cell membranes. To date, seven AQPs have been found to be expressed in mammal kidneys. The cellular localization and regulation of the transport properties of AQPs in the kidney have been widely investigated. Autophagy is known as a highly conserved lysosomal pathway, which degrades cytoplasmic components. Through basal autophagy, kidney cells maintain their functions and structure. As a part of the adaptive responses of the kidney, autophagy may be altered in response to stress conditions. Recent studies revealed that autophagic degradation of AQP2 in the kidney collecting ducts leads to impaired urine concentration in animal models with polyuria. Therefore, the modulation of autophagy could be a therapeutic approach to treat water balance disorders. However, as autophagy is either protective or deleterious, it is crucial to establish an optimal condition and therapeutic window where autophagy induction or inhibition could yield beneficial effects. Further studies are needed to understand both the regulation of autophagy and the interaction between AQPs and autophagy in the kidneys in renal diseases, including nephrogenic diabetes insipidus.

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AQP2 trafficking in health and diseases: an updated overview

Cited by 12 publications

References 175 publications

Mechanisms of aquaporin‐4 vesicular trafficking in mammalian cells

Mechanisms of aquaporin‐4 vesicular trafficking in mammalian cells

Aquaporins and Neuropathic Pain

Autophagy and regulation of aquaporins in the kidneys

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