title: Four 5-hydroxytryptamine7 (5-HT7) receptor isoforms in human and rat produced by alternative splicing: species differences due to altered intron-exon organization.
abstract: The serotonin (5-HT) 5-HT7 receptor subtype is thought to mediate a number of physiological effects in mammalian brain and periphery. Previous studies suggested that alternative splicing might contribute to 5-HT7 receptor diversity as well. We now report that alternative splicing in human and rat tissues produces four 5-HT7 receptor isoforms that differ in their predicted C-terminal intracellular tails. Human and rat partial 5-HT7 cDNAs and intronic sequences were identified and compared. In rat tissues, three 5-HT7 isoforms, here called 5-HT7(a), 5-HT7(b), and 5-HT7(c), are found. Rat 5-HT7(a) [448-amino acid (aa)] and 5-HT7(b) (435-aa) forms arise from alternative splice donor sites. A third new isoform found in rat, 5-HT7(c) (470-aa), results from a retained exon cassette. Three 5-HT7 mRNA isoforms were also identified in human tissues, where only one isoform was previously described. Two human isoforms represent 5-HT7(a) and 5-HT7(b) forms (445- and 432-aa), but the third form does not correspond to 5-HT7(c). Instead, it constitutes a distinct isoform, 5-HT7(d) (479-aa), resulting from retention of a separate exon cassette. 5-HT7(d) transcripts are not present in rat because the 5-HT7(d)-specifying exon is absent from the rat 5-HT7 gene. A frame-shifting homologue of the rat 5-HT7(c)-Specifying exon is present in the human gene but is not used in the human tissues examined. Tissue-specific splicing differences are present in human between brain and spleen. These studies suggest that alternative splicing may contribute to diversity of 5-HT7 receptor action and that the human and rat repertoires of 5-HT7 splice variants are substantially different.
authors.affiliation: Geriatric Research, Education and Clinical Center (GRECC), Seattle Veterans Affairs Medical Center, WA 98108, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Heidmann
authors.forename: M A
authors.initials: MA
authors.lastname: Metcalf
authors.forename: R
authors.initials: R
authors.lastname: Kohen
authors.forename: M W
authors.initials: MW
authors.lastname: Hamblin
mesh_terms: D017398:Alternative Splicing / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002421:Caudate Nucleus / Q000737:chemistry; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D005091:Exons / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry; D006801:Humans; D007438:Introns / Q000235:genetics; D007536:Isomerism; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011985:Receptors, Serotonin / Q000737:chemistry* / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D013154:Spleen / Q000737:chemistry
chemical_list: D012333:RNA, Messenger; D011985:Receptors, Serotonin