Department of Biochemistry and Molecular Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Dev Dyn. 2011 Dec;240(12):2601-12. doi: 10.1002/dvdy.22721. Epub 2011 Oct 25.
The novel adaptor protein Kazrin associates with multifunctional entities including p120-subfamily members (ARVCF-, delta-, and p0071-catenin). Critical contributions of Kazrin to development or homeostasis are indicated with respect to ectoderm formation, integrity and keratinocyte differentiation, whereas its presence in varied tissues suggests broader roles. We find that Kazrin is maternally loaded, is expressed across development and becomes enriched in the forming head. Kazrin's potential contributions to craniofacial development were probed by means of knockdown in the prospective anterior neural region. Cartilaginous head structures as well as eyes on injected sides were reduced in size, with molecular markers suggesting an impact upon neural crest cell establishment and migration. Similar effects followed the depletion of ARVCF (or delta-catenin), with Kazrin:ARVCF functional interplay supported upon ARVCF partial rescue of Kazrin knockdown phenotypes. Thus, Kazrin and its associating ARVCF- and delta-catenins, are required to form craniofacial tissues originating from cranial neural crest and precordal plate.
新型衔接蛋白 Kazrin 与多种多功能实体相关联,包括 p120 亚家族成员(ARVCF-、delta- 和 p0071-连环蛋白)。鉴于其在表皮形成、完整性和角质形成细胞分化方面的重要作用,可以推断 Kazrin 对发育和体内平衡有重要贡献,而其在各种组织中的存在表明它具有更广泛的作用。我们发现 Kazrin 是母源性的,在发育过程中表达,并在形成的头部中富集。通过在预期的前神经区域敲低 Kazrin 来探究其对颅面发育的潜在贡献。注射侧的软骨头部结构和眼睛的大小减小,分子标记表明其对神经嵴细胞的建立和迁移有影响。在 ARVCF(或 delta-连环蛋白)耗竭后也出现了类似的影响,Kazrin:ARVCF 功能相互作用得到了 ARVCF 部分挽救 Kazrin 敲低表型的支持。因此,Kazrin 及其关联的 ARVCF 和 delta-连环蛋白对于源自颅神经嵴和心前板的颅面组织的形成是必需的。