Kazrin regulates keratinocyte cytoskeletal networks, intercellular junctions and differentiation.
Kazrin is an evolutionarily conserved protein that is upregulated during keratinocyte terminal differentiation. Kazrin localizes to desmosomes and binds the epidermal cornified envelope protein periplakin. Kazrin overexpression in human epidermal keratinocytes caused profound changes in cell shape, reduced filamentous actin, reorganized keratin filaments, and impaired assembly of intercellular junctions. These effects were attributable to decreased Rho activity in kazrin-overexpressing cells. Kazrin overexpression also stimulated terminal differentiation and reduced clonal growth in culture. Knockdown of kazrin decreased expression of differentiation markers and stimulated proliferation without changing total Rho activity. We conclude that kazrin is a dual regulator of intercellular adhesion and differentiation in keratinocytes and regulates these processes by Rho-dependent and -independent mechanisms.
Epithelial Cell Biology Laboratory, Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.
Lisa M
LM
Sevilla
Rachida
R
Nachat
Karen R
KR
Groot
Fiona M
FM
Watt
D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007365:Intercellular Junctions; D047908:Intracellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D034622:RNA Interference; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D000199:Actins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C492711:KAZN protein, human; D008565:Membrane Proteins; D020741:rho GTP-Binding Proteins; D002118:Calcium