DEFINITION
Aquaporins are proteins embedded in the cell membrane that regulate the flow of water.
Aquaporins are integral membrane proteins from a larger family of major intrinsic proteins (MIP) that form pores in the membrane of biological cells.
Their classical role in facilitating trans-epithelial fluid transport is well understood, as in the urinary concentrating mechanism and gland fluid secretion. AQPs are also involved in swelling of tissues under stress, as in the injured cornea and the brain in stroke, tumor and infection. Recent analysis of AQP-knockout mice has revealed unexpected cellular roles of AQPs. AQPs facilitate cell migration, as manifested by reduced tumor angiogenesis in AQP1-knockout mice, by a mechanism that might involve facilitated water transport in lamellipodia of migrating cells. AQPs that transport both glycerol and water regulate glycerol content in epidermis and fat, and consequently skin hydration/biosynthesis and fat metabolism. AQPs might also be involved in neural signal transduction, cell volume regulation and organellar physiology. (More than just water channels: unexpected cellular roles of aquaporins,2005)
THE GENE
.
| Tissue | AQP0 | AQP1 | AQP2 | AQP3 | AQP4 | AQP5 | AQP6 | AQP7 | AQP8 | AQP9 | AQP10 | AQP11 | AQP12A | AQP12B |
| brain | . | . | . | . | x | AQP5 | AQP6 | AQP7 | AQP8 | AQP9 | AQP10 | AQP11 | AQP12A | AQP12B |
CHEMICAL STRUCTURE AND IMAGES
When relevant for the function
- Primary structure
- Secondary structure
- Tertiary structure
- Quaternary structure
The AQPs are proteins that assemble in cell membranes as tetramers. Each monomer is 30 kDa and has six membrane spanning domains surrounding a water pore that can transport water in both directions.
Protein Aminoacids Percentage
The Protein Aminoacids Percentage gives useful information on the local environment and the metabolic status of the cell (starvation, lack of essential AA, hypoxia)
Protein Aminoacids Percentage (Width 700 px)
On the basis of Glu/Gln ratio, AQP1 is the most ancient AQP.
SYNTHESIS AND TURNOVER
mRNA synthesis
protein synthesis
post-translational modifications
degradation
CELLULAR FUNCTIONS
cellular localization
- transmembrane integral protein
0. Water channel. May be responsible for regulating the osmolarity of the lens. Interactions between homotetramers from adjoining membranes may stabilize cell junctions in the eye lens core
1. Expressed in a number of tissues including erythrocytes, renal tubules, retinal pigment epithelium, heart, lung, skeletal muscle, kidney and pancreas. Weakly expressed in brain, placenta and liver.
2. Expressed in renal collecting tubules.
3. Widely expressed in epithelial cells of kidney (collecting ducts) and airways, in keratinocytes, immature dendritic cells and erythrocytes. Isoform 2 is not detectable in erythrocytes at the protein level.
4. Brain - muscle >> heart, kidney, lung, and trachea.
5. carbon dioxide transport
6. Forms a water-specific channel that participates in distinct physiological functions such as glomerular filtration, tubular endocytosis and acid-base metabolism By similarity. Cytoplasmic vesicle membrane; Multi-pass membrane protein
7. Forms a channel for water and glycerol.
8. Forms a water-specific channel; mercury-sensitive. Not permeable to glycerol or urea. Expressed only in pancreas and colon.
9. Forms a channel with a broad specificity. Mediates passage of a wide variety of non-charged solutes including carbamides, polyols, purines, and pyrimidines in a phloretin- and mercury-sensitive manner, whereas amino acids, cyclic sugars, Na+, K+, Cl-, and deprotonated monocarboxylates are excluded. Also permeable to urea and glycerol. Highly expressed in peripheral leukocytes. Also expressed in liver, lung, and spleen.
10. Water channel required to promote glycerol permeability and water transport across cell membranes. May contribute to water transport in the upper portion of small intestine. Isoform 2 is not permeable to urea and glycerol. Expressed exclusively in duodenum and jejunum. Highest expression in absorptive epithelial cells at the tips of villi in the jejunum.
11. Aquaporins facilitate the transport of water and small neutral solutes across cell membranes
12A. Restricted to the pancreas.
12B. Aquaporins facilitate the transport of water and small neutral solutes across cell membranes
biological function
- Forms a water-specific channel that provides the plasma membranes of red cells and kidney proximal tubules with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient.
- Cell signaling and Ligand transport
- Structural proteins
REGULATION
DIAGNOSTIC USE
BRAIN
Water and Ion Channels: Crucial in the Initiation and Progression of Apoptosis in Central Nervous System?, 2008
[Aquaporin water channels in the brain and molecular mechanisms of brain edema].
[Article in Japanese] 2008
Aquaporins(AQPs) are a family of water selective channel. Transcripts of AQP1, AQP3, AQP4, AQP5, AQP8, and AQP9 are detected in the brain. Especially in astrocytes, AQP4 is abundantly expressed in end feet at the blood-brain barrier. Brain AQPs play important roles in the regulation of water homeostasis and the cerebro spinal fluid formation. Recently, AQP4 and AQP9 have been reported to involve in the brain water accumulation in the brain edema. Studies of transgenic mouse and brain injury models reveal that AQP4 may play a role not in the edema formation, but in the fluid elimination. Further study of AQPs functions in the brain may provide new insights into the brain edema and allow the design of novel anti edema medications.
Migraine associated with water deprivation and progressive myopia. 2005
Defective hepatocyte aquaporin-8 expression and reduced canalicular membrane water permeability in estrogen-induced cholestasis 2006
Aquaporin-4 autoantibodies in a paraneoplastic context. 2008
Thyroid hormone stimulates the renal Na/H exchanger NHE3 by transcriptional activation 1999
Renal expression of sodium transporters and aquaporin-2 in hypothyroid rats 2003
Hypothyroidism (induced by methimazole):
- high aquaporin 2
- low Na/H exchanger NHE3 and NaPi2
Disruption of aquaporin-11 produces polycystic kidneys following vacuolization of the proximal tubule. 2005
Effect of the excess of thyroid hormone administration on water and sodium chloride intake in the rat. 1988
- By using the two-bottle, self-selection method it was found that an excess of thyroid hormone administration to rats increased water and sodium intake. Thyroidectomy changed the initial preference from water to sodium chloride. Oral treatment of the thyroidectomized rats with thyroid hormones brought salt ingestion back to normal levels and greatly augmented the water intake. Two-week treatment was followed by an increase in salt intake, which was characterized by large oscillations resembling the corresponding effects of adrenalectomy and treatment with deoxycorticosterone.
Acquaporine2
http://www.lescienze.it/news/2002/04/21/news/la_danza_dell_acqua-589672/
http://www.vglobale.it/index.php?option=com_content&view=article&id=3469&catid=805%3Aper-saperne-di-piu&Itemid=2&lang=it
http://host.uniroma3.it/dipartimenti/biologia/new_sito_bio/materiale/citologia/lezioni2008/membrane2.pdf
http://pipialetto.net/medic/pato/05.htm
Il ruolo della acquaporina2 (AQP2) è, invece, strettamente correlato all’ormone
vasopressina, deputato alla regolazione dell’escrezione dell’acqua.
http://it.wikipedia.org/wiki/Vasopressina
Struttura e correlazione con l'Ossitocina [modifica]
Le vasopressine (vasopressina umana e gli analoghi ormoni presenti in altre specie
animali) sono dei peptidi formati da 9 aminoacidi (nonapeptide). Il numero di
aminoacidi presenti nella molecola di preormone prima che questa venga attivata per
clivaggio è di 164. La sequenza aminoacidica (struttura primaria) della
vasopressina umana è Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-Gly con i residui di cisteina
legati da un ponte disolfuro. La lisin-vasopressina ha l'aminoacido lisina al posto
dell'arginina.
La struttura dell'Ossitocina è molto simile a quella delle vasopressine: anch'essa
è un nonapeptide (peptide di nove aminoacidi) con un ponte disolfuro e la sua
sequenza aminoacidica differisce solo in due posizioni (vedi tabella seguente). Il
gene che codifica per la vasopressina e il gene che codifica per l'ossitocina si
trovano sullo stesso cromosoma separati da una distanza relativamente breve (meno di
15,000 basi nelle varie specie). I neuroni magnocellulari che producono vasopressina
sono simili in molti aspetti e adiacenti ai neuroni magnocellulari che producono
ossitocina. La somiglianza tra vasopressina ed ossitocina può determinare reazioni
crociate: l'ossitocina presenta una bassa attività antidiuretica, alti livelli di
vasopressina possono determinare contrazioni della muscolatura uterina.
P3H2_HUMAN
uno dei geni che causano la miopia é il gene Leprel1, spiega Ohad Birk
dell’Università di Ben-Gurion nel Negev. Il gene serve a produrre un enzima
fondamentale per dare la forma giusta al bulbo oculare. Se l’enzima non funziona
il collagene si deposita nell’occhio in modo aberrante e il bulbo oculare si
allunga più del dovuto. L’allungamento del bulbo oculare genera la miopia perchè
impedisce una corretta messa a fuoco in quanto l’immagine non si forma sulla
retina ma davanti ad essa, risultando sfocata.
eye aquaporin ?
myopia more aquaporin ?
Aquaporin 4
Neuron-Astrocyte Interactions: Partnership for Normal Function and Disease in the Central Nervous System 2005
Astrocyte metabolism and signaling during brain ischemia 2007
ALLPLUS Aquaporin and Mitochondria
More than just water channels: unexpected cellular roles of aquaporins 2005
Aquaporins (AQPs) are membrane proteins that transport water and, in some cases, also small solutes such as glycerol. AQPs are expressed in many fluid-transporting tissues, such as kidney tubules and glandular epithelia, as well as in non-fluid-transporting tissues, such as epidermis, adipose tissue and astroglia. Their classical role in facilitating trans-epithelial fluid transport is well understood, as in the urinary concentrating mechanism and gland fluid secretion. AQPs are also involved in swelling of tissues under stress, as in the injured cornea and the brain in stroke, tumor and infection. Recent analysis of AQP-knockout mice has revealed unexpected cellular roles of AQPs. AQPs facilitate cell migration, as manifested by reduced tumor angiogenesis in AQP1-knockout mice, by a mechanism that might involve facilitated water transport in lamellipodia of migrating cells. AQPs that transport both glycerol and water regulate glycerol content in epidermis and fat, and consequently skin hydration/biosynthesis and fat metabolism. AQPs might also be involved in neural signal transduction, cell volume regulation and organellar physiology. The many roles of AQPs could be exploited for clinical benefit; for example, treatments that modulate AQP expression/function could be used as diuretics, and in the treatment of brain swelling, glaucoma, epilepsy, obesity and cancer.ù
