TI  - Making a connection: direct binding between keratin intermediate filaments
      and desmosomal proteins.
PG  - 1049-60
AB  - In epidermal cells, keratin intermediate filaments connect with desmosomes
      to form extensive cadherin-mediated cytoskeletal architectures.
      <prot>Desmoplakin</prot> (<prot>DPI</prot>), a desmosomal component lacking a transmembrane domain,
      has been implicated in this interaction, although most studies have been
      conducted with cells that contain few or no desmosomes, and efforts to
      demonstrate direct interactions between desmoplakin and intermediate
      filaments have not been successful. In this report, we explore the
      biochemical nature of the connections between keratin filaments and
      desmosomes in epidermal keratinocytes. We show that the carboxy terminal
      &quot;tail&quot; of   <prot>DPI</prot>  associates directly with the amino terminal &quot;head&quot; of  type
      II epidermal keratins , including  <prot>K1</prot> ,  <prot>K2</prot> ,  <prot>K5</prot> , and  <prot>K6</prot> . We have engineered
      and purified recombinant <prot>K5</prot> head and <prot>DPI</prot> tail, and we demonstrate direct
      interaction in vitro by solution-binding assays and by ligand blot assays.
      This marked association is not seen with simple epithelial type II
      keratins, <prot>vimentin</prot>, or with type I keratins, providing a possible
      explanation for the greater stability of the epidermal keratin filament
      architecture over that of other cell types. We have identified an 18-amino
      acid residue stretch in the <prot>K5</prot> head that is conserved only among type II
      epidermal keratins and that appears to play some role in <prot>DPI</prot> tail binding.
      This finding might have important implications for understanding a recent
      point mutation found within this binding site in a family with a
      blistering skin disorder.
AD  - Howard Hughes Medical Institute, Department of Molecular Genetics and Cell
