MOLECULAR-CLONING AND CHARACTERIZATION OF AN AQUAPORIN CDNA FROM SALIVARY, LACRIMAL, AND RESPIRATORY TISSUES

The Aquaporin family of water channels plays a fundamental role in tra nsmembrane water movements in numerous plant and animal tissues. Since the molecular pathway by which water is secreted by salivary glands i s unknown, a cDNA was isolated from rat submandibular gland by homolog y cloning. Similar to other Aquaporins, the salivary cDNA encodes a 26 5-residue polypeptide with six putative transmembrane domains separate d by five connecting loops (A-E); the NH2- and COOH-terminal halves of the polypeptide are sequence-related, and each contains the motif Asn -Pro Ala. A mercurial-inhibition site is present in extracellular loop E, and cytoplasmic loop D contains a cAMP-protein kinase phosphorylat ion consensus. In vitro translation yielded a 27-kDa polypeptide, and expression of the cRNA in Xenopus oocytes conferred a 20- fold increas e in osmotic water permeability (P-f) which was reversibly inhibited b y 1 mM HgCl2. Northern analysis demonstrated a 1.6-kilobase mRNA in su bmandibular, parotid, and sublingual salivary glands, lacrimal gland, eye, trachea, and lung. In situ hybridization revealed a strong hybrid ization over the corneal epithelium in eye and over the secretory lobu les in salivary glands. These studies have identified a new mammalian member of the Aquaporin water channel family (gene symbol AQP5) which is implicated in the generation of saliva, tears, and pulmonary secret ions.