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Structure and function of desmosomal transmembrane core and plaque molecules
A P Kowalczyk1, T S Stappenbeck, D A Parry
1Northwestern University Medical School, Department of Pathology, Chicago, IL 60611.
Biophysical Chemistry
|May 1, 1994
Summary
Desmosomes, crucial for cell adhesion, utilize desmogleins and desmoplakins (DPs). The DP C-terminus specifically binds keratin intermediate filaments (IF), anchoring them to the desmosome.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Desmosomes are key intercellular junctions mediating cell-cell adhesion and anchoring intermediate filaments (IF) to the cell surface.
- Desmogleins and desmocollins form the transmembrane adhesion complex, while desmoplakins (DPs) constitute the cytoplasmic plaque.
- Desmosomal cadherins, like desmogleins, share structural similarities with classical cadherins, featuring extracellular domains, a transmembrane domain, and a cytoplasmic tail.
Purpose of the Study:
- To investigate the role of desmoplakin's C-terminus in intermediate filament attachment to desmosomes.
- To identify specific regions within desmoplakin critical for keratin and vimentin intermediate filament interaction.
- To explore potential desmosomal targeting sequences within desmoplakin.
Main Methods:
- Generation of stable cell lines expressing desmoglein 1 to study desmosomal adhesion.
- Analysis of predicted desmoplakin I sequence for homodimerization and domain structure.
- Ectopic expression of desmoplakin polypeptides to assess intermediate filament alignment in cultured cells.
Main Results:
- The C-terminus of desmoplakin I contains homology regions involved in intermediate filament organization, shared with bullous pemphigoid antigen and plectin.
- Ectopically expressed desmoplakin C-termini align with keratin and vimentin IF, while deletions abolish this interaction.
- Specific residues (48-68) within the desmoplakin C-terminus are critical for keratin IF alignment, and an N-terminal sequence is necessary for plaque incorporation.
Conclusions:
- The C-terminus of desmoplakin plays a vital role in attaching intermediate filaments to desmosomes, with a specific site mediating keratin IF interaction.
- A unique N-terminal sequence in desmoplakin may function as a desmosomal targeting signal, distinguishing it from related proteins.
- Understanding these interactions provides insight into desmosome assembly and function in maintaining tissue integrity.