Linked Life Data

19096775

Source:http://linkedlifedata.com/resource/pubmed/id/19096775

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
190
pubmed:dateCreated
2008-12-19
pubmed:abstractText
Principal cells lining renal collecting ducts control the fine-tuning of body water homeostasis by regulating water reabsorption through the water channels aquaporin-2 (AQP2), aquaporin-3 (AQP3), and aquaporin-4 (AQP4). While the localization of AQP2 is subject to regulation by arginine-vasopressin (AVP), AQP3 and AQP4 are constitutively expressed in the basolateral plasma membrane. AVP adjusts the amount of AQP2 in the plasma membrane by triggering its redistribution from intracellular vesicles into the plasma membrane. This permits water entry into the cells and water exit through AQP3 and AQP4. The translocation of AQP2 is initiated by an increase in cAMP following V2R activation through AVP. The AVP-induced rise in cAMP activates protein kinase A (PKA), which in turn phosphorylates AQP2, and thereby triggers the redistribution of AQP2. Several proteins participating in the control of cAMP-dependent AQP2 trafficking have been identified; for example, A kinase anchoring proteins (AKAPs) tethering PKA to cellular compartments; phosphodiesterases (PDEs) regulating the local cAMP level; cytoskeletal components such as F-actin and microtubules; small GTPases of the Rho family controlling cytoskeletal dynamics; motor proteins transporting AQP2-bearing vesicles to and from the plasma membrane for exocytic insertion and endocytic retrieval; SNAREs inducing membrane fusions, hsc70, a chaperone, important for endocytic retrieval. In addition, cAMP-independent mechanisms of translocation mainly involving the F-actin cytoskeleton have been uncovered. Defects of AQP2 trafficking cause diseases such as nephrogenic diabetes insipidus (NDI), a disorder characterized by a massive loss of hypoosmotic urine.This review summarizes recent data elucidating molecular mechanisms underlying the trafficking of AQP2. In particular, we focus on proteins involved in the regulation of trafficking, and physiological and pathophysiological stimuli determining the cellular localization of AQP2. The identification of proteins and protein-protein interactions may lead to the development of drugs targeting AQP2 trafficking. Such drugs may be suitable for the treatment of diseases associated with dysregulation of body water homeostasis, including NDI or cardiovascular diseases (e.g., chronic heart failure) where the AVP level is elevated, inducing excessive water retention.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0171-2004
pubmed:author
pubmed:issnType
Print
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
133-57
pubmed:meshHeading
pubmed-meshheading:19096775-A Kinase Anchor Proteins, pubmed-meshheading:19096775-Animals, pubmed-meshheading:19096775-Aquaporin 2, pubmed-meshheading:19096775-Arginine Vasopressin, pubmed-meshheading:19096775-Calcium, pubmed-meshheading:19096775-Cell Compartmentation, pubmed-meshheading:19096775-Cell Membrane, pubmed-meshheading:19096775-Cyclic AMP, pubmed-meshheading:19096775-Cytoskeleton, pubmed-meshheading:19096775-Diabetes Insipidus, Nephrogenic, pubmed-meshheading:19096775-Endocytosis, pubmed-meshheading:19096775-Homeostasis, pubmed-meshheading:19096775-Humans, pubmed-meshheading:19096775-Kidney Tubules, Collecting, pubmed-meshheading:19096775-Phosphoric Diester Hydrolases, pubmed-meshheading:19096775-Phosphorylation, pubmed-meshheading:19096775-Protein Transport, pubmed-meshheading:19096775-Signal Transduction, pubmed-meshheading:19096775-Water, pubmed-meshheading:19096775-Water-Electrolyte Balance
pubmed:year
2009
pubmed:articleTitle
Regulation of aquaporin-2 trafficking.
pubmed:affiliation
Leibniz-Institut für Molekulare Pharmakologie (FMP), Campus Berlin-Buch, Berlin, 13125, Germany.
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't