SASH1 regulates melanocyte transepithelial migration through a novel G¦Ás-SASH1-IQGAP1-E-Cadherin dependent pathway

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• 作者：Ding'an Zhou^a ; ¹ ; Zhiyun Wei^a ; ^b ; ¹ ; Shanshan Deng^a ; ^c ; ¹ ; Teng Wang^a ; Meiqing Zai^a ; Honglian Wang^a ; Luo Guo^a ; Junyu Zhang^a ; Hailei Zhong^a ; Lin He^a ; ^b ; ^d ; ^{helinhelin@gmail.com} ; Qinghe Xing^a ; ^{xingqinghef@gmail.com}
• 关键词：SASH1 ; Mutation ; Melanocyte migration ; G¦Ás ; IQGAP1
• 刊名：Cellular Signalling
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：25
• 期：6
• 页码：1526-1538
• 全文大小：3045 K

文摘

One important function of melanocytes (MCs) is to produce and transfer melanin to neighbouring keratinocytes (KCs) to protect epithelial cells from UV radiation. The mechanisms regulating the specific migration and localisation of the MC lineage remain unknown. We have found three heterozygous mutations that cause amino acid substitutions in the SASH1 gene in individuals with a kind of dyschromatosis. In epidermal tissues from an affected individual, we observed the increased transepithelial migration of melanocytes. Functional analyses indicate that these SASH1 mutations not only cause the increased migration of A375 cells and but also induce intensive bindings with two novel cell adhesion partners IQGAP1 and G¦Ás. Further, SASH1 mutations induce uniform loss of E-Cadherin in human A375 cells. Our findings suggest a new scaffold protein SASH1 to regulate IQGAP1-E-Cadherin signalling and demonstrate a novel crosstalking between GPCR signalling, calmodulin signalling for the modulation of MCs invasion.