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Plectin-Isoform-Specific Rescue of Hemidesmosomal Defects in Plectin (–/–) Keratinocytes
- Source :
- Journal of Investigative Dermatology. 120(2):189-197
- Publication Year :
- 2003
- Publisher :
- Elsevier BV, 2003.
-
Abstract
- The various plectin isoforms are among the major crosslinking elements of the cytoskeleton. The importance of plectin in epithelia is convincingly supported by the severe skin blistering observed in plectin-deficient humans and mice. Here, we identified plectin 1a (> 500 kDa), a full length plectin variant containing the sequence encoded by the alternative first exon 1a, as the isoform most prominently expressed in human and mouse keratinocytes. In skin sections and cultured keratinocytes, plectin 1a was shown to colocalize with hemidesmosomal structures. In contrast, a second isoform expressed in epithelia, plectin 1c, differing from 1a merely by a short N-terminal sequence, colocalized with microtubules. Expression of plectin 1a, but not of its N-terminal fragment alone, or of a third alternative full length isoform (plectin 1), restored the reduced number of hemidesmosome-like stable anchoring contacts in cultured plectin-null keratinocytes. Our results show for the first time that different isoforms of a cytolinker protein expressed in one cell type perform distinct functions. Moreover, the identification of plectin 1a as the isoform defects in which cause skin blistering in plectin-related genetic diseases, such as epidermolysis bullosa simplex MD and epidermolysis bullosa simplex Ogna, could have implications for the future development of clinical therapies for patients.
- Subjects :
- Keratinocytes
Gene isoform
muscular dystrophy
Cell type
epidermolysis bullosa simplex
macromolecular substances
Dermatology
Biology
Transfection
Biochemistry
Mice
Epidermolysis bullosa simplex
Exon
Blister
Intermediate Filament Proteins
Isomerism
Desmosome
medicine
Animals
Molecular Biology
Cytoskeleton
Cell Line, Transformed
cytolinkers
Alternative splicing
Desmosomes
Exons
Plectin
Cell Biology
medicine.disease
Mice, Mutant Strains
Peptide Fragments
Cell biology
Alternative Splicing
medicine.anatomical_structure
Immunology
plakins/plectin isoforms
Keratinocyte
Subjects
Details
- ISSN :
- 0022202X
- Volume :
- 120
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of Investigative Dermatology
- Accession number :
- edsair.doi.dedup.....d1330a568b861e43899ab17d81f7a284
- Full Text :
- https://doi.org/10.1046/j.1523-1747.2003.12027.x