title: Identification and characterization of new functional truncated variants of somatostatin receptor subtype 5 in rodents.
abstract: Somatostatin and cortistatin exert multiple biological actions through five receptors (sst1-5); however, not all their effects can be explained by activation of sst1-5. Indeed, we recently identified novel truncated but functional human sst5-variants, present in normal and tumoral tissues. In this study, we identified and characterized three novel truncated sst5 variants in mice and one in rats displaying different numbers of transmembrane-domains [TMD; sst5TMD4, sst5TMD2, sst5TMD1 (mouse-variants) and sst5TMD1 (rat-variant)]. These sst5 variants: (1) are functional to mediate ligand-selective-induced variations in [Ca(2+)]i and cAMP despite being truncated; (2) display preferential intracellular distribution; (3) mostly share full-length sst5 tissue distribution, but exhibit unique differences; (4) are differentially regulated by changes in hormonal/metabolic environment in a tissue- (e.g., central vs. systemic) and ligand-dependent manner. Altogether, our results demonstrate the existence of new truncated sst5-variants with unique ligand-selective signaling properties, which could contribute to further understanding the complex, distinct pathophysiological roles of somatostatin and cortistatin.
authors.affiliation: Department of Cell Biology, Physiology and Immunology, University of Córdoba, Edificio Severo Ochoa. Planta 3. Campus de Rabanales, 14014 Córdoba, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Córdoba-Chacón
authors.forename: Manuel D
authors.initials: MD
authors.lastname: Gahete
authors.forename: Mario
authors.initials: M
authors.lastname: Duran-Prado
authors.forename: Ana I
authors.initials: AI
authors.lastname: Pozo-Salas
authors.forename: María M
authors.initials: MM
authors.lastname: Malagón
authors.forename: F
authors.initials: F
authors.lastname: Gracia-Navarro
authors.forename: Rhonda D
authors.initials: RD
authors.lastname: Kineman
authors.forename: Raul M
authors.initials: RM
authors.lastname: Luque
authors.forename: Justo P
authors.initials: JP
authors.lastname: Castaño
mesh_terms: D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D007031:Hypothalamus / Q000378:metabolism; D008024:Ligands; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010911:Pituitary Neoplasms / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D020033:Protein Isoforms; D017481:Receptors, Somatostatin; C094573:somatostatin receptor 5; D000242:Cyclic AMP; D002118:Calcium