BPAG1e Maintains Keratinocyte Polarity through beta 4 Integrin-mediated Modulation of Rac 1 and Cofilin Activities

作者：Hamill Kevin J; Hopkinson Susan B; DeBiase Philip; Jones Jonathan C R^*

来源：Molecular Biology of the Cell, 2009, 20(12): 2954-2962.

DOI：10.1091/mbc.E09-01-0051

alpha 6 beta 4 integrin, a component of hemidesmosomes, also plays a role in keratinocyte migration via signaling through Rac1 to the actin-severing protein cofilin. Here, we tested the hypothesis that the beta 4 integrin-associated plakin protein, bullous pemphigoid antigen 1e (BPAG1e) functions as a scaffold for Rac1/cofilin signal transduction. We generated keratinocyte lines exhibiting a stable knockdown in BPAG1e expression. Knockdown of BPAG1e does not affect expression levels of other hemidesmosomal proteins, nor the amount of beta 4 integrin expressed at the cell surface. However, the amount of Rac1 associating with beta 4 integrin and the activity of both Rac1 and cofilin are significantly lower in BPAG1e-deficient cells compared with wild-type keratinocytes. In addition, keratinocytes deficient in BPAG1e exhibit loss of front-to-rear polarity and display aberrant motility. These defects are rescued by inducing expression of constitutively active Rac1 or active cofilin. These data indicate that the BPAG1e is required for efficient regulation of keratinocyte polarity and migration by determining the activation of Rac1.

• 出版日期2009-6-15
• 单位西北大学