The rod domain is not essential for the function of plectin in maintaining tissue integrity.

Abstract

Epidermolysis bullosa simplex associated with late-onset muscular dystrophy (EBS-MD) is an autosomal recessive disorder resulting from mutations in the plectin gene. The majority of these mutations occur within the large exon 31 encoding the central rod domain and leave the production of a low-level rodless plectin splice variant unaffected. To investigate the function of the rod domain, we generated rodless plectin mice through conditional deletion of exon 31. Rodless plectin mice develop normally without signs of skin blistering or muscular dystrophy. Plectin localization and hemidesmosome organization are unaffected in rodless plectin mice. However, superresolution microscopy revealed a closer juxtaposition of the C-terminus of plectin to the integrin β4 subunit in rodless plectin keratinocytes. Wound healing occurred slightly faster in rodless plectin mice than in wild-type mice, and keratinocytes migration was increased in the absence of the rod domain. The faster migration of rodless plectin keratinocytes is not due to altered biochemical properties because, like full-length plectin, rodless plectin is a dimeric protein. Our data demonstrate that rodless plectin can functionally compensate for the loss of full-length plectin in mice. Thus the low expression level of plectin rather than the absence of the rod domain dictates the development of EBS-MD.

• Authors: Mirjam Ketema, Pablo Secades, Maaike Kreft, Leila Nahidiazar, Hans Janssen, Kees Jalink, Jose M de Pereda, Arnoud Sonnenberg
• Journal: Molecular biology of the cell (Mol Biol Cell) Vol. 26 Issue 13 Pg. 2402-17 (Jul 01 2015) ISSN: 1939-4586 [Electronic] United States
• PMID: 25971800 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Ketema et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Chemical References

• Integrin beta4
• Plectin
• Protein Isoforms

Topics

• Animals
• Cytoskeleton (metabolism, pathology)
• Epidermolysis Bullosa Simplex (genetics, metabolism, pathology)
• Female
• Hemidesmosomes (metabolism)
• Integrin beta4 (metabolism)
• Keratinocytes (metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Models, Animal
• Muscular Dystrophies, Limb-Girdle (genetics, metabolism, pathology)
• Plectin (genetics, metabolism)
• Protein Isoforms
• Protein Structure, Tertiary