Two distinct genes drive expression of seven tomosyn isoforms in the mammalian brain, sharing a conserved structure with a unique variable domain

J Neurochem. 2005 Feb;92(3):554-68. doi: 10.1111/j.1471-4159.2004.02890.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics
  • Amino Acid Sequence
  • Animals
  • Brain / embryology
  • Brain / metabolism*
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics*
  • Cloning, Molecular
  • Conserved Sequence / genetics*
  • Gene Expression Regulation, Developmental
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics*
  • Organ Specificity / genetics
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • Protein Structure, Tertiary / genetics
  • R-SNARE Proteins
  • RNA, Messenger / biosynthesis
  • Retina / embryology
  • Retina / metabolism
  • Sequence Homology, Amino Acid
  • Spinal Cord / embryology
  • Spinal Cord / metabolism
  • Vesicular Transport Proteins / biosynthesis*
  • Vesicular Transport Proteins / genetics*

Substances

  • Carrier Proteins
  • Nerve Tissue Proteins
  • Protein Isoforms
  • R-SNARE Proteins
  • RNA, Messenger
  • STXBP5L protein, mouse
  • Vesicular Transport Proteins
  • tomosyn protein, mouse