BPAG1e maintains keratinocyte polarity through beta4 integrin-mediated modulation of Rac1 and cofilin activities.

Abstract	alpha6beta4 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 beta4 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 beta4 integrin expressed at the cell surface. However, the amount of Rac1 associating with beta4 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.
Authors	Kevin J Hamill, Susan B Hopkinson, Philip DeBiase, Jonathan C R Jones
Journal	Molecular biology of the cell (Mol Biol Cell) Vol. 20 Issue 12 Pg. 2954-62 (Jun 2009) ISSN: 1939-4586 [Electronic] United States
PMID	19403692 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	Actin Depolymerizing Factors Actins Carrier Proteins Cytoskeletal Proteins DST protein, human Dystonin Integrin beta4 Nerve Tissue Proteins Plectin RNA, Small Interfering rac1 GTP-Binding Protein
Topics	Actin Depolymerizing Factors (metabolism) Actins (metabolism) Carrier Proteins (metabolism) Cell Line Cell Movement Cell Polarity Cytoskeletal Proteins (deficiency, metabolism) Cytoskeleton (metabolism) Dystonin Enzyme Activation Epidermal Cells Focal Adhesions (metabolism) Gene Knockdown Techniques Humans Integrin beta4 (metabolism) Keratinocytes (cytology, metabolism) Lentivirus (genetics) Nerve Tissue Proteins (deficiency, metabolism) Plectin (metabolism) Protein Transport Pseudopodia (metabolism) RNA, Small Interfering (metabolism) rac1 GTP-Binding Protein (metabolism)

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