A Role for DLK in Microtubule Reorganization to the Cell Periphery and in the Maintenance of Desmosomal and Tight Junction Integrity

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• 作者：Carolyne Simard-Bisson¹ ; ² ; Julie Bidoggia¹ ; Danielle Larouche¹ ; ² ; Sylvain L. Gué ; rin¹ ; ³ ; ⁴ ; Richard Blouin⁵ ; Syu-Ichi Hirai⁶ ; ⁷ ; Lucie Germain¹ ; ² ; ⁴ ; ^{lucie.germain@fmed.ulaval.ca}
• 关键词：Actub ; acetylated α-tubulin ; AdDLK ; DLK/GFP expressing adenoviral vector ; AdGFP ; GFP expressing adenoviral vector ; A/L ; air liquid ; CIF ; cytoskeleton-enriched insoluble fraction ; Ctl ; control ; DLK ; dual leucine zipper-bearing kinase ; GFP ; green fluorescent protein ; HSP27 ; heat shock protein 27 kDa ; LIS1 ; lissencephaly-1 protein ; LV ; lentiviral vector ; MT ; microtubule ; NHK ; normal human keratinocyte ; TES ; tissue-engineered skin
• 刊名：Journal of Investigative Dermatology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：137
• 期：1
• 页码：132-141
• 全文大小：5429 K
• 卷排序：137

文摘

Dual leucine zipper-bearing kinase (DLK) is an inducer of keratinocyte differentiation, a complex process also involving microtubule reorganization to the cell periphery. However, signaling mechanisms involved in this process remain to be elucidated. Here, we demonstrate that DLK enhances and is required for microtubule reorganization to the cell periphery in human cell culture models and in Dlk knockout mouse embryos. In tissue-engineered skins with reduced DLK expression, cortical distribution of two microtubule regulators, LIS1 and HSP27, is impaired as well as desmosomal and tight junction integrity. Altered cortical distribution of desmosomal and tight junction proteins was also confirmed in Dlk knockout mouse embryos. Finally, desmosomal and tight junction defects were also observed after microtubule disruption in nocodazole-treated tissue-engineered skins, thus confirming a role for microtubules in the maintenance of these types of cell junctions. Globally, this study demonstrates that DLK is a key regulator of microtubule reorganization to the cell periphery during keratinocyte differentiation and that this process is required for the maintenance of desmosomal and tight junction integrity.