An emerging consensus on aquaporin translocation as a regulatory mechanism

Figures & data

Table I. Tissue distribution and functional roles of the 13 human AQPs. The Table summarizes the distribution and function of AQPs in specific cells and tissues of the human body. Immunohistochemistry has revealed the diversity of AQP distribution within cells and tissues. For example, AQPs 1, 2, 3, 4, 6, 7, 8, 9, 10 and 11 have all been shown to be expressed in tissues of the kidney whereas AQP0 is almost exclusively expressed in lens epithelial cells. AQP11 expression in leucocytes may explain the immunohistochemical identification of AQP11 in other tissues.

AQP	Location	Putative functional roles
0	Lens fibre gap junctions	Water regulation, structural function
1	Kidney (proximal renal tubule), eye, CNS, lung, erythrocytes	Water homeostasis, fluid reabsorption
2	Kidney collecting duct	Water homeostasis, reabsorption from urine
3	Kidney, epithelial cells	Water homeostasis in renal collecting duct, glycerol/lipid metabolism
4	Glial cells, (astrocytes), renal collecting duct	Water regulation
5	Salivary glands, lung, eye	Facilitates isotonic secretions
6	Renal collecting duct	Intracellular water/ion regulation
7	Adipocytes, kidney, liver, testis	Glycerol/lipid metabolism
8	Liver, kidney, testis, pancreas, heart, colon, placenta	Water homeostasis
9	Kidney, liver, leucocytes, lung, spleen, brain, testis	Water/small molecule homeostasis, glycerol metabolism
10	Small intestine (duodenum, jejunum), kidney	Water regulation
11	Kidney, testis, brain, pancreas, leucocytes, smooth muscle	Unknown
12	Pancreas	Unknown

Figure 1. Schematic diagram of the shared structural architecture of aquaporins. Six transmembrane α-helices are connected by alternating extracellular and intracellular loops with the carboxyl and amino termini orientated towards the cytoplasm. Two of these connecting loops (B and E) fold into the transmembrane pore so that the protein resembles an hour-glass. Loops B and E each form a helical region containing highly conserved Asn-Pro-Ala (NPA) motifs that facilitate selectivity of the pore. The approximate positions of serine or threonine protein kinase phosphorylation sites involved in AQP translocation are indicated as follows; ▴ = Ser²³⁵ in AQP0; ⧫ = Thr¹⁵⁷ and ○ = Thr²³⁹ in AQP1; □ = Ser²⁵⁶ in AQP2; = Ser¹¹¹ and = Ser¹⁸⁰ in AQP4; = Ser¹⁵² in AQP5; = Ser¹¹ and ▵ = Ser²²² in AQP9.

Table II. Triggers of aquaporin translocation to the plasma membrane (PM). The Table summarizes known stimuli of the dynamic translocation of AQPs, where possible avoiding observations solely linked to water permeability (WP) and/or transcription/translation. The experimental system used to determine the AQP translocation is included for each trigger.

Trigger	AQP	Translocation	Experimental system	Reference
Vasopressin	AQP2 AQP4	PM WP	Native kidney tissue Xenopus oocytes	(Christensen et al. 2000) (Moeller et al. 2009)
Histamine	AQP4	PM	Human gastric cells	(Carmosino et al. 2007)
Isoprenaline	AQP3 AQP7	PM PM	Human adipocytes Human adipocytes	(Rodriguez et al. 2011b) (Rodriguez et al. 2011b)
Secretin	AQP1	PM	Cholangiocytes	(Marinelli et al. 1997)
Vasoactive intestinal polypeptide	AQP5	PM	Duodenum (Brunner's gland)	(Parvin et al. 2005)
Adrenaline	AQP3 AQP5	PM PM	Caco-2 epithelial cells Rat parotid cells	(Yasui et al. 2008) (Ishikawa et al. 1999)
Glutamate	AQP4	PM/WP	Astrocytes	(Gunnarson et al. 2008)
Acetylcholine	AQP5	PM	Rat parotid cells	(Ishikawa et al. 1998b)
Lipopolysaccharide	AQP5	PM	Lung epithelial cells	(Ohinata et al. 2005)
Hypotonicity	AQP1 AQP3 AQP8	PM PM PM	HEK293/astrocytes Keratinocytes Amnion epithelial cells	(Conner et al. 2010) (Garcia et al. 2011) (Qi et al. 2009)
Hypertonicity	AQP1 AQP2 AQP3 AQP4 AQP5 AQP9	PM PM PM PM PM PM	Human neutrophils Collecting duct cells MDCK cells Rat astrocytes Lung epithelial cells Rat astrocytes	(Loitto et al. 2007) (Hasler et al. 2005) (Matsuzaki et al. 2001) (Arima et al. 2003) (Hoffert et al. 2000) (Arima et al. 2003)

Table III. Intracellular components involved in the translocation of specific aquaporins to the plasma membrane (PM). The Table summarizes the components of dynamic translocation of AQPs avoiding, where possible, observations solely linked to water permeability (WP) and/or transcription/translation. Arrows indicate the direction of the effect. The experimental system used to determine the AQP translocation is included for each trigger and the residue that the component acts upon is also included where known. †Residues in PKC. *AQP2 is not added in more detail than PKA-linked as this has been very well reviewed elsewhere (Valenti et al. 2005).

Intracellular component	AQP	Effect	Experimental system	Residue	Reference
PKA	AQP0 AQP2* AQP4 AQP5 AQP5 AQP6 AQP7	↓WP ↑PM ↓PM ↓PM ↑PM None Putative	Collecting duct Kidney tissue Human gastric cells MDCK Brunner's gland MDCK n/a	S235 S256 - S152 - - -	(Reichow and Gonen 2008) (Christensen et al. 2000) (Carmosino et al. 2007) (Karabasil et al. 2009) (Parvin et al. 2005) (Beitz et al. 2006) (Kishida et al. 2000)
PKC	AQP0 AQP1 AQP3 AQP3 AQP4 AQP4 AQP9	↑PM ↑PM ↑PM ↓PM ↑PM ↓PM ↑PM	RK13 epithelial cells HEK293 cells Caco-2 epithelial cells Caco-2 epithelial cells Astrocytes Xenopus oocytes Human neutrophils	S235 T157/T239 T514† S660† S111 S180 S11	(Golestaneh et al. 2008) (Conner et al. 2012) (Yasui et al. 2008) (Yasui et al. 2008) (Gunnarson et al. 2008) (Moeller et al. 2009) (Karlsson et al. 2011)
PKG	AQP5	↑PM	Rat parotid cells	-	(Ishikawa et al. 2002)
Actin	AQP1 AQP4 AQP5 AQP5	↑PM ↑PM ↑PM ↑PM	Cholangiocytes Astrocytes Salivary gland cells Rat parotid	- - - -	(Tietz et al. 2006) (Nicchia et al. 2008) (Tada et al. 1999) (Ishikawa et al. 1999)
Microtubule + cAMP	AQP1 AQP5 AQP8 AQP5	↑PM ↑PM ↑PM ↑PM	HEK293 cells MDCK cells Hepatocytes Lung epithelial cells	- - - -	(Conner et al. 2010) (Karabasil et al. 2009) (Garcia et al. 2001) (Yang et al. 2003)
Ca2+/ Calmodulin	AQP1 AQP5 AQP6	↑PM ↑PM ↑PM	HEK293 cells Rat parotid cells CHO-K1 cells	- - -	(Conner et al. 2012) (Ishikawa et al. 1998a, 1999, Rabaud et al. 2009)
TRP channels	AQP1	↑PM	HEK293 cells	-	(Conner et al. 2012)
RAC1	AQP9	↑PM	Human neutrophils	-	(Karlsson et al. 2011)
Dynein	AQP1	↑PM	Cholangiocytes	-	(Marinelli et al. 1997)
Kinesin	AQP1	↑PM	Cholangiocytes	-	(Marinelli et al. 1997)

Figure 2. Trigger-induced aquaporin translocation: a regulatory mechanism for cellular water flow. Some or all of the components shown may be involved in the translocation of different AQPs. For example, AQP1 translocation is known to be triggered by hypotonicity, which causes calcium influx through transient receptor potential (TRP) channels and subsequent calmodulin-mediated PKC phosphorylation of specific AQP1 threonine residues, resulting in microtubule-dependent AQP1 translocation. Other protein kinases are thought to be involved in AQP translocation such as PKA-mediated translocation of AQP2 and AQP5 following activation of vasopressin V2 and M3 muscarinic GPCRs, respectively.

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