Aqp4
Developmental stage
Detected in mature brain, but not in fetal brain.
Domain
Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).
Function
Forms a water-specific channel (PubMed:19800950, PubMed:7509789, PubMed:7528931). Plays an important role in brain water homeostasis and in glymphatic solute transport. Required for a normal rate of water exchange across the blood brain interface. Required for normal levels of cerebrospinal fluid influx into the brain cortex and parenchyma along paravascular spaces that surround penetrating arteries, and for normal drainage of interstitial fluid along paravenous drainage pathways. Thereby, it is required for normal clearance of solutes from the brain interstitial fluid, including soluble beta-amyloid peptides derived from APP. Plays a redundant role in urinary water homeostasis and urinary concentrating ability (By similarity).
Post-translational modifications
Phosphorylation by PKC at Ser-180 promotes internalization from the cell membrane, reducing the conductance by 50% (PubMed:19800950). Phosphorylation by PKG at Ser-111 in response to glutamate increases conductance by 40% (By similarity).
Isoform Long: Palmitoylated on its N-terminal region. Isoform 3: Not palmitoylated.
Sequence Similarities
Belongs to the MIP/aquaporin (TC 1.A.8) family.
Tissue Specificity
Detected in cerebellum (PubMed:18179769, PubMed:29055082). Detected on pericapillary astrocyte endfeet in cerebellum, and in skeletal muscle (PubMed:29055082). Detected in glial lamellae in the hypothalamus (at protein level) (PubMed:16325200). Abundant in mature brain cortex, cerebellum and spinal cord. Highly expressed in the ependymal cell lining the aqueductal system and over the space of the brain in contact with the subarachnoid space. Detected in paraventricular and supraoptic nuclei, the granule cell layer of the dentate gyrus and the Purkinje cell layer in the cerebellum. Only weakly detectable in eye, kidney, intestine, and lung (PubMed:7528931).
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Basolateral cell membrane
- Multi-pass membrane protein
- Endosome membrane
- Cell membrane
- Sarcolemma
- Multi-pass membrane protein
- Cell projection
- Activation of the vasopressin receptor AVPR1A triggers AQP4 phosphorylation at Ser-180 and promotes its internalization from the cell membrane (PubMed:19800950). Detected on brain astrocyte processes and astrocyte endfeet close to capillaries (PubMed:29055082).
Alternative names
Aquaporin-4, AQP-4, Mercurial-insensitive water channel, WCH4, MIWC, Aqp4