title: 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.affiliation: Division of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Ketema
authors.affiliation: Division of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
authors.forename: Pablo
authors.initials: P
authors.lastname: Secades
authors.affiliation: Division of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
authors.forename: Maaike
authors.initials: M
authors.lastname: Kreft
authors.affiliation: Division of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
authors.forename: Leila
authors.initials: L
authors.lastname: Nahidiazar
authors.affiliation: Division of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Janssen
authors.affiliation: Division of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands.
authors.forename: Kees
authors.initials: K
authors.lastname: Jalink
authors.affiliation: Instituto de Biología Molecular y Celular del Cancer, University of Salamanca-CSIC, E-37007 Salamanca, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: de Pereda
authors.affiliation: Division of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, Netherlands a.sonnenberg@nki.nl.
authors.forename: Arnoud
authors.initials: A
authors.lastname: Sonnenberg
mesh_terms: D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism / Q000473:pathology; D016110:Epidermolysis Bullosa Simplex / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D022002:Hemidesmosomes / Q000378:metabolism; D039663:Integrin beta4 / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051190:Plectin / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary
chemical_list: D039663:Integrin beta4; D051190:Plectin; D020033:Protein Isoforms