Polarized trafficking and surface expression of the AQP4 water channel are coordinated by serial and regulated interactions with different clathrin-adaptor complexes.
Ricardo Madrid,Sophie Le Maout,Marie-Bénédicte Barrault,Katy Janvier,Serge Benichou,Jean Mérot +5 more
TLDR
It is shown that two independent C‐terminal signals determine AQP4 basolateral membrane targeting in epithelial MDCK cells, and stress‐induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQp4–μ3A interaction and enhancing AQP 4–lysosomal targeting and degradation.Abstract:
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 mu subunit of AP2 adaptor complex. Once endocytosed, a regulated switch in mu 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-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. AQP4 phosphorylation by CKII may thus provide a mechanism that regulates AQP4 cell surface expression.read more
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Signals for Sorting of Transmembrane Proteins to Endosomes and Lysosomes
TL;DR: This work has shown that peptide motifs serve as a signal for sorting at various stages of the endosomal-lysosomal system and several proteins, including clathrin, AP-2, and Dab2, have been proposed to function as recognition proteins for NPXY signals.
Journal ArticleDOI
One-thousand-and-one substrates of protein kinase CK2?
Flavio Meggio,Lorenzo A. Pinna +1 more
TL;DR: An analysis of 308 sites phosphorylated by CK2 highlights the paramount relevance of negatively charged side chains that are (by far) predominant over any other residues at positions n+3 (the most crucial one), n+1, and n+2.
Journal ArticleDOI
From structure to disease: the evolving tale of aquaporin biology
TL;DR: This work states that the discovery of aquaporins has stimulated a reconsideration of membrane water permeability by investigators across a wide range of disciplines and indicates diverse roles in the regulation of water homeostasis.
Journal ArticleDOI
A method for the comprehensive proteomic analysis of membrane proteins
TL;DR: A method that allows for the concurrent proteomic analysis of both membrane and soluble proteins from complex membrane-containing samples and coupling protease protection strategies to this method permits characterization of the relative sidedness of the hydrophilic domains of membrane proteins.
Journal ArticleDOI
Physiological Roles of Aquaporin-4 in Brain
TL;DR: A review will be provided of the physiological roles of AQP4 in brain and of the growing list of data that emphasize the polarized nature of astrocytes.
References
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Journal ArticleDOI
Aquaporin-4 deletion in mice reduces brain edema after acute water intoxication and ischemic stroke.
Geoffrey T. Manley,Miki Fujimura,Tonghui Ma,Nobuo Noshita,Ferda Filiz,Andrew W. Bollen,Pak H. Chan,Alan S. Verkman +7 more
TL;DR: It is shown that mice deficient in aquaporin-4 (AQP4), a glial membrane water channel, have much better survival than wild-type mice in a model of brain edema caused by acute water intoxication, and suggested that AQP4 inhibition may provide a new therapeutic option for reducingbrain edema in a wide variety of cerebral disorders.
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Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance
TL;DR: Its distinctive expression pattern implicates this fourth mammalian member of the aquaporin water channel family (designated gene symbol, AQP4) as the osmoreceptor which regulates body water balance and mediates water flow within the central nervous system.
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Direct immunogold labeling of aquaporin-4 in square arrays of astrocyte and ependymocyte plasma membranes in rat brain and spinal cord
TL;DR: Evidence is provided that AQP4 is concentrated in glial square arrays in astrocyte and ependymocyte plasma membranes in rat brain and spinal cord, and freeze-fracture methods may now provide biophysical insights regarding neuropathological states in which abnormal fluid shifts are accompanied by alterations in the aggregation state or the molecular architecture of square arrays.
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The Shank family of scaffold proteins
Morgan Sheng,Eunjoon Kim +1 more
TL;DR: The specific localization of Shank proteins at postsynaptic sites of brain excitatory synapses suggests a role for this family of proteins in the organization of cytoskeletal/ signaling complexes at specialized cell junctions.
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New Perspectives on Mechanisms Involved in Generating Epithelial Cell Polarity
TL;DR: It is proposed that the establishment of structural asymmetry in the plasma membrane is the first, critical event, and subsequently, this asymmetry is reinforced and maintained by delivery of proteins that were constitutively sorted in the Golgi.