KazrinE is a desmosome-associated liprin that colocalises with acetylated microtubules.
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.
Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Cambridge, CB2 0RE, UK.
Rachida
R
Nachat
Sara
S
Cipolat
Lisa M
LM
Sevilla
Mariya
M
Chhatriwala
Karen R
KR
Groot
Fiona M
FM
Watt
D000107:Acetylation; D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D048430:Cell Shape; D003598:Cytoskeletal Proteins; D003896:Desmosomes / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000502:physiology* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D051179:Plakins / Q000378:metabolism; D020033:Protein Isoforms; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4 / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C492711:KAZN protein, human; D008565:Membrane Proteins; C094398:PPFIA1 protein, human; C491674:PPL protein, human; D051179:Plakins; D020033:Protein Isoforms; C519285:Kazn protein, mouse; C516841:PTPRA protein, human; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4