Plectin expression patterns determine two distinct subtypes of epidermolysis bullosa simplex

Ken Natsuga, Wataru Nishie, Masashi Akiyama, Hideki Nakamura, Satoru Shinkuma, James R. McMillan, Akari Nagasaki, Cristina Has, Takeshi Ouchi, Akira Ishiko, Yoshiaki Hirako, Katsushi Owaribe, Daisuke Sawamura, Leena Bruckner-Tuderman, Hiroshi Shimizu

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Plectin is a cytoskeletal linker protein that has a dumbbell-like structure with a long central rod and N- and C-terminal globular domains. Mutations in the gene encoding plectin (PLEC1) cause two distinct autosomal recessive subtypes of epidermolysis bullosa (EB): EB simplex with muscular dystrophy (EBS-MD), and EB simplex with pyloric atresia (EBS-PA). Here, we demonstrate that normal human fibroblasts express two different plectin isoforms including full-length and rodless forms of plectin. We performed detailed analysis of plectin expression patterns in six EBS-MD and three EBS-PA patients. In EBS-PA, expression of all plectin domains was found to be markedly attenuated or completely lost; in EBS-MD, the expression of the N- and C-terminal domains of plectin remained detectable, although the expression of rod domains was absent or markedly reduced. Our data suggest that loss of the full-length plectin isoform with residual expression of the rodless plectin isoform leads to EBS-MD, and that complete loss or marked attenuation of full-length and rodless plectin expression underlies the more severe EBS-PA phenotype. These results also clearly account for the majority of EBS-MD PLEC1 mutation restriction within the large exon 31 that encodes the plectin rod domain, whereas EBS-PA PLEC1 mutations are generally outside exon 31.

Original languageEnglish
Pages (from-to)308-316
Number of pages9
JournalHuman Mutation
Volume31
Issue number3
DOIs
Publication statusPublished - 2010 Mar

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Plectin
Epidermolysis Bullosa Simplex
Muscular Dystrophies
Protein Isoforms
Mutation
Exons
Plakins
Epidermolysis Bullosa

Keywords

  • Basement membrane zone
  • mRNA decay
  • PLEC1
  • Skeletal muscle
  • Truncation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Natsuga, K., Nishie, W., Akiyama, M., Nakamura, H., Shinkuma, S., McMillan, J. R., ... Shimizu, H. (2010). Plectin expression patterns determine two distinct subtypes of epidermolysis bullosa simplex. Human Mutation, 31(3), 308-316. https://doi.org/10.1002/humu.21189

Plectin expression patterns determine two distinct subtypes of epidermolysis bullosa simplex. / Natsuga, Ken; Nishie, Wataru; Akiyama, Masashi; Nakamura, Hideki; Shinkuma, Satoru; McMillan, James R.; Nagasaki, Akari; Has, Cristina; Ouchi, Takeshi; Ishiko, Akira; Hirako, Yoshiaki; Owaribe, Katsushi; Sawamura, Daisuke; Bruckner-Tuderman, Leena; Shimizu, Hiroshi.

In: Human Mutation, Vol. 31, No. 3, 03.2010, p. 308-316.

Research output: Contribution to journalArticle

Natsuga, K, Nishie, W, Akiyama, M, Nakamura, H, Shinkuma, S, McMillan, JR, Nagasaki, A, Has, C, Ouchi, T, Ishiko, A, Hirako, Y, Owaribe, K, Sawamura, D, Bruckner-Tuderman, L & Shimizu, H 2010, 'Plectin expression patterns determine two distinct subtypes of epidermolysis bullosa simplex', Human Mutation, vol. 31, no. 3, pp. 308-316. https://doi.org/10.1002/humu.21189
Natsuga K, Nishie W, Akiyama M, Nakamura H, Shinkuma S, McMillan JR et al. Plectin expression patterns determine two distinct subtypes of epidermolysis bullosa simplex. Human Mutation. 2010 Mar;31(3):308-316. https://doi.org/10.1002/humu.21189
Natsuga, Ken ; Nishie, Wataru ; Akiyama, Masashi ; Nakamura, Hideki ; Shinkuma, Satoru ; McMillan, James R. ; Nagasaki, Akari ; Has, Cristina ; Ouchi, Takeshi ; Ishiko, Akira ; Hirako, Yoshiaki ; Owaribe, Katsushi ; Sawamura, Daisuke ; Bruckner-Tuderman, Leena ; Shimizu, Hiroshi. / Plectin expression patterns determine two distinct subtypes of epidermolysis bullosa simplex. In: Human Mutation. 2010 ; Vol. 31, No. 3. pp. 308-316.
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