Kazrin regulates keratinocyte cytoskeletal networks, intercellular junctions and differentiation

被引:33
作者
Sevilla, Lisa M. [1 ,2 ,3 ]
Nachat, Rachida [1 ]
Groot, Karen R. [4 ]
Watt, Fiona M. [1 ,2 ,3 ]
机构
[1] Canc Res UK Cambridge Res Inst, Epithelial Cell Biol Lab, Li Ka Shing Ctr, Cambridge CB2 0RE, England
[2] Univ Cambridge, Wellcome Trust Ctr Stem Cell Res, Cambridge CB2 1QR, England
[3] Univ Cambridge, Dept Genet, Cambridge CB2 1QR, England
[4] Natl Inst Canc Res, London WC2A 3PX, England
基金
美国国家卫生研究院; 英国惠康基金;
关键词
Rho GTPases; Cytoskeleton; Desmosomes; Keratinocyte; Terminal differentiation;
D O I
10.1242/jcs.029538
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:3561 / 3569
页数:9
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