Polarized trafficking and surface expression of the AQP4 water channel are coordinated by serial and regulated interactions with different clathrin–adaptor complexes
AUTOR(ES)
Madrid, Ricardo
FONTE
Oxford University Press
RESUMO
Aquaporin 4 (AQP4) is the predominant water channel in the brain. It is targeted to specific membrane domains of astrocytes and plays a crucial role in cerebral water balance in response to brain edema formation. AQP4 is also specifically expressed in the basolateral membranes of epithelial cells. However, the molecular mechanisms involved in its polarized targeting and membrane trafficking remain largely unknown. Here, we show that two independent C-terminal signals determine AQP4 basolateral membrane targeting in epithelial MDCK cells. One signal involves a tyrosine-based motif; the other is encoded by a di-leucine-like motif. We found that the tyrosine-based basolateral sorting signal also determines AQP4 clathrin-dependent endocytosis through direct interaction with the µ subunit of AP2 adaptor complex. Once endocytosed, a regulated switch in µ subunit interaction changes AP2 adaptor association to AP3. We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4–µ3A interaction and enhancing AQP4–lysosomal targeting and degradation. AQP4 phosphorylation by CKII may thus provide a mechanism that regulates AQP4 cell surface expression.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=125333Documentos Relacionados
- The AP-1 Clathrin-adaptor Is Required for Lysosomal Enzymes Sorting and Biogenesis of the Contractile Vacuole Complex in Dictyostelium Cells
- The human AQP4 gene: definition of the locus encoding two water channel polypeptides in brain.
- Interactions of the Cytoplasmic Domains of Human and Simian Retroviral Transmembrane Proteins with Components of the Clathrin Adaptor Complexes Modulate Intracellular and Cell Surface Expression of Envelope Glycoproteins
- An α-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain
- Cloning and expression of AQP3, a water channel from the medullary collecting duct of rat kidney.