title: Aquaporin-2 trafficking is regulated by PDZ-domain containing protein SPA-1.
abstract: Targeted positioning of water channel aquaporin-2 (AQP2) strictly regulates body water homeostasis. Trafficking of AQP2 to the apical membrane is critical to the reabsorption of water in renal collecting ducts. Controlled apical positioning of AQP2 suggests the existence of proteins that interact with AQP2. A biochemical search for AQP2-interacting proteins led to the identification of PDZ-domain containing protein, signal-induced proliferation-associated gene-1 (SPA-1) which is a GTPase-activating protein (GAP) for Rap1. The distribution of SPA-1 coincided with that of AQP2 in renal collecting ducts. The site of colocalization was concomitantly relocated by hydration status. AQP2 trafficking to the apical membrane was inhibited by the SPA-1 mutant lacking Rap1GAP activity and by the constitutively active mutant of Rap1. AQP2 trafficking was impaired in SPA-1-deficient mice. Our results show that SPA-1 directly binds to AQP2 and regulates at least in part AQP2 trafficking.
authors.affiliation: Department of Homeostasis Medicine and Nephrology, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan. ynodmed2@tmd.ac.jp
authors.forename: Yumi
authors.initials: Y
authors.lastname: Noda
authors.forename: Saburo
authors.initials: S
authors.lastname: Horikawa
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Furukawa
authors.forename: Keiji
authors.initials: K
authors.lastname: Hirai
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Katayama
authors.forename: Tomoki
authors.initials: T
authors.lastname: Asai
authors.forename: Michio
authors.initials: M
authors.lastname: Kuwahara
authors.forename: Koko
authors.initials: K
authors.lastname: Katagiri
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kinashi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Hattori
authors.forename: Nagahiro
authors.initials: N
authors.lastname: Minato
authors.forename: Sei
authors.initials: S
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D051399:Aquaporin 2; D020346:Aquaporins / Q000378:metabolism*; D002460:Cell Line; D004285:Dogs; D005455:Fluorescent Antibody Technique; D008969:Molecular Sequence Data; D021381:Protein Transport / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism
chemical_list: C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D020346:Aquaporins; D020827:rap1 GTP-Binding Proteins