Actinin-4 in keratinocytes regulates motility via an effect on lamellipodia stability and matrix adhesions

作者：Hamill Kevin J; Hopkinson Susan B; Skalli Omar; Jones Jonathan C R^*

来源：The FASEB Journal, 2013, 27(2): 546-556.

DOI：10.1096/fj.12-217406

• focal contact
• hemidesmosome
• laminin
• integrin

During wound repair, epidermal cells at the edge of an injury establish front-rear polarity through orchestrated changes in their cytoskeleton and adhesion structures. The polarity and directed migration of such cells is determined by the assembly, extension, and stabilization of a lamellipodium. Actinin-4 associates with lamellipodia and has been implicated in regulating lamellipodial structure, function and assembly. To study the functions of actinin-4 in human keratinocytes, we used shRNA to generate knockdown cells and compared their motility behavior and matrix adhesion assembly to scrambled shRNA treated control keratinocytes. Actinin-4 knockdown keratinocytes lack polarity, assemble multiple lamellipodia with a 2 x increased area over controls, display reduced activity of the actin remodeling protein cofilin, and fail to migrate in a directional manner. This motility defect is rescued by plating knockdown cells on preformed laminin-332 matrix. In actinin-4-knockdown keratinocytes, focal contact area is increased by 25%, and hemidesmosome proteins are mislocalized. Specifically, alpha 6 beta 4 integrin localizes to large lamellipodial extensions, displays reduced dynamics, and fails to recruit its bullous pemphigoid antigen binding partners. Together, our data indicate a role for actinin-4 in regulating the steering mechanism of keratinocytes via profound effects on their matrix adhesion sites.-Hamill, K. J., Hopkinson, S. B., Skalli, O., Jones, J. C. R. Actinin-4 in keratinocytes regulates motility via an effect on lamellipodia stability and matrix adhesions. FASEB J. 27, 546-556 (2013). www.fasebj.org

• 出版日期2013-2
• 单位西北大学