title: The zinc sensing receptor, ZnR/GPR39, in health and disease.
abstract: While zinc has had a well-established structural role for many years, it is only during the last two decades that its role as a signaling molecule has been recognized. Ionic zinc, Zn2+, that is endogenously released during physiological activity acts as a first messenger, triggering the activity of a distinct Zn2+-sensing-receptor, ZnR. The ZnR is a member of the Gq-coupled receptor family, and the molecular moiety mediating its activity is GPR39. In this review, we will discuss the role of the ZnR/GPR39 in mediating Zn2+-dependent signaling in epithelial tissues and in neurons, where Zn2+homeostasis plays physiological as well as pathological roles. Importantly, ZnR/GPR39 activates signaling that regulates a remarkably wide range of cell functions, including proliferation, differentiation and survival, as well as modulation of ion transport, and thereby, regulation of Na+, H+and Cl-homeostasis. Moreover, signaling activated by ZnR/GPR39 plays a key role in mediating effects of Zn2+in health and disease. Thus, ZnR/GPR39 provides a unique target for therapeutically modifying the actions of zinc in a specific and selective manner.
authors.affiliation: Department of Physiology and Cell Biology and The Zlotowski Center for Neuroscience, Faculty of Health Sciences, Ben-Gurion university of the Negev, Beer Sheva, Israel.
authors.forename: Laxmi
authors.initials: L
authors.lastname: Sunuwar
authors.affiliation: Department of Physiology and Cell Biology and The Zlotowski Center for Neuroscience, Faculty of Health Sciences, Ben-Gurion university of the Negev, Beer Sheva, Israel.
authors.forename: David
authors.initials: D
authors.lastname: Gilad
authors.affiliation: Department of Physiology and Cell Biology and The Zlotowski Center for Neuroscience, Faculty of Health Sciences, Ben-Gurion university of the Negev, Beer Sheva, Israel, hmichal@bgu.ac.il.
authors.forename: Michal
authors.initials: M
authors.lastname: Hershfinkel
mesh_terms: D000818:Animals; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D012640:Seizures / Q000378:metabolism; D015398:Signal Transduction; D015032:Zinc / Q000378:metabolism*
chemical_list: C495797:GPR39 protein, human; D018377:Neurotransmitter Agents; D043562:Receptors, G-Protein-Coupled; D015032:Zinc