title: Two distinct genes drive expression of seven tomosyn isoforms in the mammalian brain, sharing a conserved structure with a unique variable domain.
abstract: Tomosyn was previously identified as a syntaxin-binding protein that inhibits soluble NSF (n-ethylmaleimide-sensitive fusion protein) attachment protein receptor (SNARE)-mediated secretion. We set out to investigate the distribution of tomosyn mRNA in the mammalian brain and found evidence for the presence of two paralogous genes designated tomosyn-1 and -2. In a collection of tomosyn-2 cDNA clones, we observed four splice variants (named xb-, b-, m- and s-tomosyn-2) derived from the skipping of exons 19 and 21. This feature is conserved with tomosyn-1 that encodes three splice variants. To compare the expression pattern of tomosyn-1 and -2, we performed in situ hybridization experiments with gene-specific probes. Both genes were expressed in the nervous system, clearly following distinct spatial and developmental expression patterns. Real-time quantitative PCR experiments indicated that tomosyn-1 expression was up-regulated less than threefold between developmental stages E10 and P12, whereas tomosyn-2 expression increased 31-fold. Not only the transcription level, but also the splice composition of tomosyn-2 mRNA shifted during development. We conclude that two distinct genes drive expression of seven tomosyn isoforms. Their expression patterns support a role in regulating neuronal secretion. All isoforms share conserved WD40 and SNARE domains separated by a hypervariable module, the function of which remains to be clarified.
authors.affiliation: Department of Functional Genomics, Center for Neurogenomics and Cognition Research, Vrije Universiteit, De Boelelaan 1085, 1081 HV Amsterdam, the Netherlands. sander@cncr.vu.nl
authors.forename: Alexander J A
authors.initials: AJ
authors.lastname: Groffen
authors.forename: Linda
authors.initials: L
authors.lastname: Jacobsen
authors.forename: Désireé
authors.initials: D
authors.lastname: Schut
authors.forename: Matthijs
authors.initials: M
authors.lastname: Verhage
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D003001:Cloning, Molecular; D017124:Conserved Sequence / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D050683:R-SNARE Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D012160:Retina / Q000196:embryology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013116:Spinal Cord / Q000196:embryology / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D050683:R-SNARE Proteins; D012333:RNA, Messenger; C492530:STXBP5L protein, mouse; D033921:Vesicular Transport Proteins; C112618:tomosyn protein, mouse