Identification and characterization of DSPIa, a novel isoform of human desmoplakin

Rita M Cabral, Hong Wan, Clare L Cole, Dominic J Abrams, David P Kelsell, Andrew P South

Research output: Contribution to journalArticle (Academic Journal)peer-review

15 Citations (Scopus)

Abstract

Desmoplakin is a ubiquitous component of desmosomes and desmosome-like structures, such as the cardiomyocyte area composita. Two major isoforms, desmoplakin I (DSPI) and desmoplakin II (DSPII) are encoded by alternative mRNA transcripts differentially spliced from the same gene. The resulting proteins are identical in amino acid sequence with the exception that DSPII contains only one third of the central alpha-helical rod domain present in DSPI. Here we describe a novel minor isoform of desmoplakin that is also produced by alternative splicing of the desmoplakin gene and that we name desmoplakin Ia (DSPIa). DSPIa is an alternatively spliced DSPI mRNA with a unique splice donor site that is 90% homologous to and downstream of the DSPII specific donor. The resulting DSPIa mRNA is in-frame and encodes a protein that has a central alpha-helical rod domain of intermediate size and that is 156 amino acids larger than DSPII and 443 amino acids smaller than DSPI. We demonstrate, through recombinant expression and short interfering RNA knockdown, that the DSPIa protein is readily detectable, albeit at substantially lower levels than the dominant isoforms, DSPI and DSPII. DSPIa mRNA has a similar tissue distribution to that of DSPI and of DSPII.

Original languageEnglish
Pages (from-to)121-9
Number of pages9
JournalCell and Tissue Research
Volume341
Issue number1
DOIs
Publication statusPublished - Jul 2010

Keywords

  • Alternative Splicing
  • Base Sequence
  • Cell Line, Tumor
  • DNA, Complementary
  • Desmoplakins
  • Epidermis
  • Expressed Sequence Tags
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Humans
  • Keratinocytes
  • Male
  • Molecular Sequence Data
  • Myocardium
  • Prostatic Neoplasms
  • Protein Isoforms
  • RNA Splice Sites
  • RNA, Small Interfering
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Nucleic Acid
  • Journal Article
  • Research Support, Non-U.S. Gov't

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