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. 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.
 ...
PMID:Identification of a multiprotein "motor" complex binding to water channel aquaporin-2. 1582 48

Mutations in CLCN5, which encodes the voltage-dependent Cl(-)/H(+)antiporter, CLC-5, cause Dent's disease. This disorder is characterized by low molecular-weight proteinuria, hypercalciuria, nephrocalcinosis and nephrolithiasis. Using a collecting duct cell model (mIMCD-3) in which endogenous clc-5 is disrupted by antisense clc-5 or overexpression of truncated clc-5, we demonstrate altered expression of the crystal adhesion molecule, annexin A2. Endogenously expressed annexin A2 is intracellular with limited plasma membrane localization. Following clc-5 disruption, there is both a marked increase in plasma membrane annexin A2 and an increase in cell surface crystal retention and agglomeration, which may be attenuated using pretreatment with anti-annexin A2 antibodies or wheat germ agglutinin lectin but not by concanavalin A. We hypothesize that in Dent's disease, endocytic failure leads to an accumulation at the plasma membrane of crystal-binding molecules that include annexin A2 leading to retention of calcium crystals and ultimately nephrocalcinosis and nephrolithiasis.
 ...
PMID:Disruption of clc-5 leads to a redistribution of annexin A2 and promotes calcium crystal agglomeration in collecting duct epithelial cells. 1642 22