Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Aquaporin-2 trafficking is regulated by PDZ-domain containing protein SPA-1. 1519 35

Targeted positioning of water channel aquaporin-2 (AQP2) strictly regulates body water homeostasis. Trafficking of AQP2 to the apical membrane is critical for the reabsorption of water in renal collecting ducts. Besides the cAMP-mediated effect of vasopressin on AQP2 trafficking to the apical membrane, other signaling cascades also induce this sorting. Recently, AQP2-binding proteins that directly regulate this trafficking have been uncovered: SPA-1, a GTPase-activating protein (GAP) for Rap1, and cytoskeletal protein actin. This review summarizes recent advances related to the trafficking mechanism of AQP2 and its defect causing nephrogenic diabetes insipidus (NDI).
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PMID:Molecular mechanisms and drug development in aquaporin water channel diseases: molecular mechanism of water channel aquaporin-2 trafficking. 1553 62

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. Recently, we have identified for the first time proteins which directly bind to AQP2: SPA-1, a GTPase-activating protein for Rap1, and cytoskeletal protein actin. Based on these findings, we have speculated the existence of a multiprotein complex which includes AQP2, SPA-1, and actin, for providing the mechanism which generates force and motion in AQP2 trafficking. To clarify the proteins comprising the complex, a large amount of AQP2-associated protein complex was isolated from the extract of rat kidney papilla using immunoaffinity column coupled with anti-AQP2 antibody and was analyzed by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). In addition to SPA-1 and actin, 11 proteins were identified using this method: ionized calcium binding adapter molecule 2, myosin regulatory light chain smooth muscle isoforms 2-A and 2-B, alpha-tropomyosin 5b, annexin A2 and A6, scinderin, gelsolin, alpha-actinin 4, alpha-II spectrin, and myosin heavy chain nonmuscle type A. Our findings show for the first time an AQP2-binding multiprotein "force generator" complex. This multiprotein complex may provide the machinery of driving AQP2 movement.
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PMID:Identification of a multiprotein "motor" complex binding to water channel aquaporin-2. 1582 48

Trafficking of water channel aquaporin-2 (AQP2) to the apical membrane is critical to water reabsorption in renal collecting ducts and its regulation maintains body water homeostasis. However, exact molecular mechanisms which recruit AQP2 are unknown. Recent studies highlighted a key role for spatial and temporal regulation of actin dynamics in AQP2 trafficking. We have recently identified AQP2-binding proteins which directly regulate this trafficking: SPA-1, a GTPase-activating protein (GAP) for Rap1, and cytoskeletal protein actin. In addition, a multiprotein "force generator" complex which directly binds to AQP2 has been discovered. This review summarizes recent advances related to the mechanism for AQP2 trafficking.
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PMID:Regulation of aquaporin-2 trafficking and its binding protein complex. 1662 55