Localization and trafficking of aquaporin 2 in the kidney

Kuniaki Takata 0 1 2 3 4 5 Toshiyuki Matsuzaki 0 1 2 3 4 5 Yuki Tajika 0 1 2 3 4 5 Abduxukur Ablimit 0 1 2 3 4 5 Takahiro Hasegawa 0 1 2 3 4 5 0 Present Address: T. Matsuzaki Department of Anatomy and Neurobiology, Nippon Medical School , Bunkyo-ku, Tokyo 113-8602, Japan 1 K. Takata (&) T. Matsuzaki Y. Tajika A. Ablimit T. Hasegawa Department of Anatomy and Cell Biology, Gunma University Graduate School of Medicine , 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan 2 Robert Feulgen Lecture presented at the 50th Symposium of the Society for Histochemistry , 1-4 October 2008, Interlaken, Switzerland 3 Present Address: T. Hasegawa Department of Molecular Oral Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School , Tokushima, Tokushima 770-8504, Japan 4 Present Address: A. Ablimit Department of Histology and Embryology, Xinjiang Medical University , Urumqi, 830054 Xinjiang, China 5 Present Address: Y. Tajika Department of Anatomy, Gunma University Graduate School of Medicine , Maebashi, Gunma 371-8511, Japan Aquaporins (AQPs) are membrane proteins serving in the transfer of water and small solutes across cellular membranes. AQPs play a variety of roles in the body such as urine formation, prevention from dehydration in covering epithelia, water handling in the bloodbrain barrier, secretion, conditioning of the sensory system, cell motility and metastasis, formation of cell junctions, and fat metabolism. The kidney plays a central role in water homeostasis in the body. At least seven isoforms, namely AQP1, AQP2, AQP3, AQP4, AQP6, AQP7, and AQP11, are expressed. Among them, AQP2, the anti-diuretic hormone (ADH)-regulated water channel, plays a critical role in water reabsorption. AQP2 is expressed in principal cells of connecting tubules and collecting ducts, where it is stored in Rab11-positive storage vesicles in the basal state. Upon ADH stimulation, AQP2 is translocated to the apical plasma membrane, where it serves in the inXux of water. The translocation process is regulated through the phosphorylation of AQP2 by protein kinase A. As soon as the stimulation is terminated, AQP2 is retrieved to early endosomes, and then transferred back to the Rab 11-positive storage compartment. Some AQP2 is secreted via multivesicular bodies into the urine as exosomes. Actin plays an important role in the intracellular traYcking of AQP2. Recent Wndings have shed light on the molecular basis that controls the traYcking of AQP2. - Aquaporins (AQPs) are membrane proteins serving in the transfer of water and small solutes across cellular membranes. A novel integral membrane protein of 28-kDa was identiWed from the human erythrocyte ghost during the isolation of the 32-kDa Rh polypeptides (Denker et al. 1988). Immunohistochemistry revealed that this 28-kDa protein was abundant in the kidney and localized in the proximal tubule cells. cDNA cloning identiWed a membrane protein with 6 membrane-spanning domains and intracellular N- and C-termini, and it was named channel-like integral protein of 28 kDa (CHIP28) due to its structural similarity to membrane channel proteins (Preston and Agre 1991). When CHIP28 was expressed in Xenopus oocytes, a mercurial-sensitive increase in the water permeability of the plasma membrane was observed, demonstrating that CHIP28 was a long-sought water channel protein (Preston et al. 1992). Water channel proteins were later named aquaporins (AQPs) (Agre et al. 1993), and CHIP28 was classiWed as AQP1. An AQP molecule is composed of approximately 270 amino acid residues. AQPs are usually glycosylated and form homotetramers in the membrane, with each having an independent channel pore for water in each monomer. Two asparagine-proline-alanine sequences, called NPA boxes, are conserved. The hourglass model of AQP predicted that two loops containing NPA boxes are folded into the center of the membrane, and form a critical portion of the pore in the channel where water molecules pass through. Crystallographic analyses using X-ray and electron beams have revealed the detailed molecular structure of AQPs (for review see Engel et al. 2008). AQPs are widely distributed among bacteria, plants, and animals (Krane and Goldstein 2007; Rojek et al. 2008; KaldenhoV et al. 2007). In mammalian cells, 13 isoforms, namely AQP0 through AQP12 have been identiWed to date (Agre et al. 2002; Matsuzaki et al. 2002; Nielsen et al. 2002; Takata et al. 2004b; Ishibashi 2006). AQPs are classiWed into three subfamilies: the aquaporin subfamily, aquaglyceroporin subfamily, and superaquaporin subfamily. The aquaporin subfamily is speciWc to water permeation, and is made up of AQP0, AQP1, AQP2, AQP4, AQP5, AQP6, and AQP8. Aquaglyceroporin serves in the transfer of water as well as small molecules such as glycerol and urea, and is made up of AQP3, AQP7, AQP9, and AQP10. The superaquaporin subfamily is composed of AQP11 and AQP12, which show a low homology (20%) with other AQPs and have poorly conserved NPA boxes (Morishita et al. 2004; Ishibashi 2006). Roles of AQPs in the body AQPs are expressed in various organs and play important roles in homeostasis of the body (Takata et al. 2004b). Some of them are summarized in the following section. AQPs in the kidney will be described and discussed in the subsequent sections. Prevention of dehydration The aquaglyceroporin AQP3 is abundantly expressed in the transitional epithelia covering the urinary tract such as the renal pelvis, urinary bladder, and proximal part of the urethra (Matsuzaki et al. 1999a). AQP3 is also found in the epidermis of the skin, airway epithelia covering the respiratory tract, and stratiWed epithelia of the digestive tract. It is localized along the plasma membrane other than the apical membrane. In cultured cells, the expression of AQP3 is induced by hypertonic stimulation (Matsuzaki et al. 2001). In addition, AQP3 expression of the epidermis in the rat commenced late in fetal life just prior to birth (Matsuzaki et al. 1999a). These observations indicate that AQP3 may provide epithelial cells with water from the subepithelial side to protect them from dehydration (Matsuzaki et al. 1999a). In fact, AQP3-null mice showed impaired skin hydration (Ma et al. 2002), which was alleviated by the administration of glycerol (Hara and Verkman 2003). These results show that AQP3 plays an important role in preventing epithelial cells from dehydration by taking up water and glycerol via AQP3 at their plasma membrane. AQP3 also serves in the proliferation of epidermal cells by facilitating the uptake of glycerol, and thereby is involved in the development of skin cancer (Hara-Chikuma and Verkman 2008; Verkman et al. 2008). Water handling in the blood-brain barrier AQP4 is abundant in astrocytes of the brain, where it is concentrated at their endfeet. Freeze-fracture replica electron microscopic examination revealed arrays of orthogonally arranged intramembranous particles at the plasma membran (...truncated)