Trends in Pharmacological Sciences
OpinionA fascinating tail: cGMP activation of aquaporin-1 ion channels
Section snippets
Protein–protein interactions of ion channels
In the Xenopus oocyte expression system, only a small proportion (∼0.002%) of the AQP1 channels that are present in the membrane appear to be available for cGMP-induced activation of the ionic conductance. However, calculations based on a quantitative model of kidney proximal tubule indicate that this contribution of channels could be physiologically relevant for modulating net Na+ reabsorption [8]. Furthermore, this small proportion of ion channels could have profound effects on membrane
Aquaporin-mediated transport
Controversies surround aquaporin-mediated transport, but it is important to recognize that diverse intracellular signaling pathways might influence channel properties, and that the various experimental findings are not necessarily mutually exclusive. The first mammalian aquaporin to be identified as an ion channel was the lens MIP AQP0, a protein that is vital in maintaining the optical clarity of the crystalline lens. Mutations in AQP0 underlie inherited autosomal dominant cataract disease in
C-terminal cyclic-nucleotide-binding domain
An amino acid sequence alignment between the C-terminal domains of AQP1 and CNG channels provides support for the existence of a portion of the cyclic-nucleotide-binding domain (CNBD) in each subunit of the AQP1 channel (Fig. 1c). The CNBD in CNG channels is a complex structure. Based on homology with Escherichia coli catabolite-gene-activator protein (CAP), for which the crystal structure is known [29], it has been suggested that the CNBD in CNG channels consists of a series of β-segments
Concluding remarks
Ion channel function in aquaporins has significance in the regulated control of water and ion fluxes across membranes, and possible functions in ligand-mediated signaling. The essential role of AQP1 in the formation of concentrated urine is evident in transgenic knockout mice that are grossly normal in survival, appearance and organ structure, but susceptible to severe dehydration when deprived of free access to water [40]. Cases of humans with homozygous mutations in AQP1, identified by the
Acknowledgements
Thanks to all the members of the laboratory for their research contributions. Supported by NIH RO1 GM59986 (AJY) and American Heart Association Desert-Mountain Affiliate Predoctoral Award (DB).
References (40)
Water and ion permeation of aquaporin-1 in planar lipid bilayers. Major differences in structural determinants and stoichiometry
J. Biol. Chem.
(2001)EphB2 guides axons at the midline and is necessary for normal vestibular function
Neuron
(2000)Identification and structure of a putative Ca2+-binding domain at the C terminus of AQP1
J. Mol. Biol.
(2002)- et al.
Protein modules as organizers of membrane structure
Curr. Opin. Cell Biol.
(1999) PSD-95 mediates formation of a functional homomeric Kir5.1 channel in the brain
Neuron
(2002)Water channel properties of major intrinsic protein of lens
J. Biol. Chem.
(1995)pH-Dependent channel activity of heterologously-expressed main intrinsic protein (MIP) from rat lens
FEBS Lett.
(2002)- et al.
Cyclic AMP levels during the maturation of Xenopus oocytes
Dev. Biol.
(1985) - et al.
Structure of a complex of catabolite gene activator protein and cyclic AMP refined at 2.5 Å resolution
J. Mol. Biol.
(1987) Molecular rearrangements in the ligand-binding domain of cyclic nucleotide-gated channels
Neuron
(1999)
Molecular mechanism for ligand discrimination of cyclic nucleotide-gated channels
Neuron
Severely impaired urinary concentrating ability in transgenic mice lacking aquaporin-1 water channels
J. Biol. Chem.
Pathophysiology of the aquaporin water channels
Annu. Rev. Physiol.
Aquaporin CHIP: the archetypal molecular water channel
Am. J. Physiol.
Novel roles for aquaporins as gated ion channels
Forskolin stimulation of water and cation permeability in aquaporin 1 water channels
Science
Cloned human aquaporin-1 is a cyclic GMP-gated ion channel
Mol. Pharmacol.
Structure of a glycerol-conducting channel and the basis for its selectivity
Science
New roles for old holes: Ion channel function in aquaporin-1
News Physiol. Sci.
Ion Channels of Excitable Membranes
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pH gradient inversion, aquaporins and cancer
2020, An Innovative Approach to Understanding and Treating Cancer: Targeting pH: From Etiopathogenesis to New Therapeutic AvenuesStructure, function and translational relevance of aquaporin dual water and ion channels
2012, Molecular Aspects of MedicineThe first discovered water channel protein, later called aquaporin 1: Molecular characteristics, functions and medical implications
2012, Molecular Aspects of MedicineCitation Excerpt :Later, several mechanisms of regulation of the AQP1 channel activities have been described. Cyclic nucleotides (mainly cGMP and indirectly also cAMP) have been shown by Yool group to activate AQP1 channels, both the water channel and the ion channel activity (reviewed in Boassa and Yool, 2002; Yool and Campbell, this issue). Zhang et al. (2007) found that AQP1 water and ion channels function is positively regulated by protein kinase C (PKC).
Regulation of brain aquaporins
2010, Neurochemistry InternationalCitation Excerpt :ANP signaling involves NO production and cGMP formation, but no report on cGMP dependence of AQP1 water permeability has been made so far. AQP1 COOH-terminus has been reported to have a homology with the substrate-selectivity subdomain of cyclic nucleotide phosphodiesterases and with cyclic-nucleotide-gated channels (Boassa and Yool, 2002), predicting the existence of a cyclic nucleotide binding domain. This finding was argued against by another group, predicting instead the existence of a Ca2+-binding site (Section 3.4.3) (Fotiadis et al., 2002).
Determination of cyclic GMP concentration using a gold nanoparticle-modified optical fiber
2010, Biosensors and BioelectronicsChapter 2 Ocular Aquaporins and Aqueous Humor Dynamics
2008, Current Topics in MembranesCitation Excerpt :Signaling pathways involving cAMP and cGMP are known to influence salt and water transport in the ciliary epithelium and RPE. Interestingly, while the AQP1 ion conductance is activated by increased cGMP (Anthony et al., 2000; Boassa and Yool, 2002), it has been suggested to be antagonized by intracellular cAMP (Yool and Stamer, 2004). Water channel activity of AQP1 is increased by PKA, suggesting that a cAMP‐responsive redistribution of AQP1 occurs by phosphorylation of AQP1 (Han and Patil, 2000).