[Regulation, structure and function of brain aquaporin].
Discovery of aquaporin water channel proteins has provided insight into the molecular mechanism of membrane water permeability. In mammalian brain, Aquaporin-4 (AQP4) is the main water channel and is distributed with highest density in the perivascular and subpial astrocyte end-feet. AQP4 is a critical component of an integrated water and potassium homeostasis. Indeed, AQP4 has been implicated in several neurologic conditions, such as brain edema, seizure and even mood disorders. Expression and regulation of AQP4 have been studied to understand the roles of AQP4 in physiological and pathological conditions. Here we discuss about the mechanisms how AQP4 is dynamically regulated at different levels; channel gating, subcellular distribution, phosphorylation, protein-protein interactions and orthogonal array formation. Interestingly, AQP4 has been identified as a target antigen of autoimmune attack in neuromyelitis optica (NMO). We have evaluated putative epitopes on AQP4 for NMO-IgG binding. We have also studied Drosophila Big Brain (Bib), since Bib has high sequence homology to AQP-4, and play an important role for Drosophila neurogenesis. AQP4 may be a potential therapeutic target in several neurologic conditions. Further studies from different aspects are required to develop new drugs against AQP4.
Masato
Yasui
Y
Department of Pharmacology, Keio School of Medicine.
D000818:Animals; D051401:Aquaporin 4 / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D001834:Body Water / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology; D002463:Cell Membrane Permeability; D015195:Drug Design; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D019964:Mood Disorders / Q000209:etiology; D009422:Nervous System Diseases / Q000188:drug therapy; D055495:Neurogenesis; D009471:Neuromyelitis Optica / Q000209:etiology; D011188:Potassium / Q000378:metabolism
D051401:Aquaporin 4; D007074:Immunoglobulin G; D011188:Potassium