Identification and characterization of new functional truncated variants of somatostatin receptor subtype 5 in rodents.
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.
Córdoba-Chacón
Jose
J
Department of Cell Biology, Physiology and Immunology, University of Córdoba, Edificio Severo Ochoa. Planta 3. Campus de Rabanales, 14014 Córdoba, Spain.
Gahete
Manuel D
MD
Duran-Prado
Mario
M
Pozo-Salas
Ana I
AI
Malagón
María M
MM
Gracia-Navarro
F
F
Kineman
Rhonda D
RD
Luque
Raul M
RM
Castaño
Justo P
JP
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*
D008024:Ligands; D020033:Protein Isoforms; D017481:Receptors, Somatostatin; C094573:somatostatin receptor 5; D000242:Cyclic AMP; D002118:Calcium