KazrinE Is a Desmosome-Associated Liprin That Colocalises With Acetylated Microtubules

J Cell Sci. 2009 Nov 15;122(Pt 22):4035-41. doi: 10.1242/jcs.047266. Epub 2009 Oct 20.

Abstract

Kazrin is a widely expressed, evolutionarily conserved cytoplasmic protein that binds the cytolinker protein periplakin. Multiple functions of kazrin have been reported, including regulation of desmosome assembly, embryonic tissue morphogenesis and epidermal differentiation. Here, we identify kazrinE as a kazrin isoform that contains a liprin-homology domain (LHD) and forms complexes with kazrinA, kazrinB and kazrinC. As predicted from the presence of the LHD, kazrinE can associate with the leukocyte common antigen-related (LAR) protein tyrosine phosphatase in a phosphorylation-dependent manner. When overexpressed in epidermal keratinocytes, kazrinE induces changes in cell shape and stimulates terminal differentiation. Like the other kazrin isoforms, kazrinE localises to the nucleus and desmosomes. However, in addition, kazrinE associates with stabilised microtubules via its LHD. During terminal differentiation, the keratinocyte microtubule network undergoes extensive reorganisation; in differentiating keratinocytes, endogenous kazrinE colocalises with microtubules, but periplakin does not. We speculate that the kazrinE-microtubule interaction contributes to the mechanism by which kazrin regulates desmosome formation and epidermal differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Motifs
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Differentiation*
  • Cell Line
  • Cell Nucleus / metabolism
  • Cell Shape
  • Cytoskeletal Proteins
  • Desmosomes / metabolism*
  • Epidermal Cells
  • Epidermis / physiology
  • Humans
  • Keratinocytes / physiology*
  • Keratinocytes / ultrastructure
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Microtubules / metabolism*
  • Plakins / metabolism
  • Protein Isoforms
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4 / metabolism
  • Sequence Homology, Amino Acid

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Membrane Proteins
  • PPFIA1 protein, human
  • PPL protein, human
  • Plakins
  • Protein Isoforms
  • kazrin protein, human
  • kazrin protein, mouse
  • PTPRA protein, human
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4