RT Journal Article
T1 Polarized trafficking and surface expression of the AQP4 water channel are coordinated by serial and regulated interactions with different clathrin-adaptor complexes
A1 Madrid González, Ricardo
A1 Le Maout, Sophie
A1 Barrault, Marie-Benedicte
A1 Janvier, Katy
A1 Benichou, Serge
A1 Merot, Jean
AB 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.
PB Oxford University Press
SN 1460-2075
YR 2001
FD 2001
LK https://hdl.handle.net/20.500.14352/97504
UL https://hdl.handle.net/20.500.14352/97504
LA eng
NO Madrid, R. «Polarized trafficking and surface expression of the AQP4 water channel are coordinated by serial and regulated interactions with different clathrin-adaptor complexes». The EMBO Journal, vol. 20, n.o 24, diciembre de 2001, pp. 7008-21. https://doi.org/10.1093/emboj/20.24.7008.
NO Euroepean Commission
DS Docta Complutense
RD 18 abr 2025