Plectin expression patterns determine two distinct subtypes of epidermolysis bullosa simplex.

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.

• Authors: 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
• Journal: Human mutation (Hum Mutat) Vol. 31 Issue 3 Pg. 308-16 (Mar 2010) ISSN: 1098-1004 [Electronic] United States
• PMID: 20052759 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2010 Wiley-Liss, Inc.

Chemical References

• Plectin
• Protein Isoforms
• RNA, Messenger

Topics

• Algorithms
• DNA Mutational Analysis
• Epidermolysis Bullosa Simplex (diagnosis, metabolism)
• Exons
• Fibroblasts (metabolism)
• Humans
• Keratinocytes (cytology)
• Microscopy, Fluorescence (methods)
• Models, Genetic
• Muscle, Skeletal (metabolism)
• Mutation
• Plectin (chemistry, metabolism)
• Protein Isoforms
• Protein Structure, Tertiary
• RNA, Messenger (metabolism)