Liu Ying, Snedecor Elizabeth R, Choi Yeon Ja, Yang Ning, Zhang Xu, Xu Yuhuan, Han Yunlin, Jones Evan C, Shroyer Kenneth R, Clark Richard A, Zhang Lianfeng, Qin Chuan, Chen Jiang
Institute of Laboratory Animal Science, Chinese Academy of Medical Science, Comparative Medical Center, Peking Union Medical College, and Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China.
Department of Pathology, Stony Brook University, Stony Brook, New York, USA; Graduate Program in Genetics, Stony Brook University, Stony Brook, New York, USA.
J Invest Dermatol. 2016 Feb;136(2):378-386. doi: 10.1016/j.jid.2015.10.067. Epub 2015 Nov 24.
GORAB is a golgin that localizes predominantly at the Golgi apparatus and physically interacts with small guanosine triphosphatases. GORAB is ubiquitously expressed in mammalian tissues, including the skin. However, the biological function of this golgin in skin is unknown. Here, we report that disrupting the expression of the Gorab gene in mice results in hair follicle morphogenesis defects that were characterized by impaired follicular keratinocyte differentiation. This hair follicle phenotype was associated with markedly suppressed hedgehog (Hh) signaling pathway in dermal condensates in vivo. Gorab-deficient dermal mesenchymal cells also displayed a significantly reduced capability to respond to Hh pathway activation in vitro. Furthermore, we found that the formation of the primary cilium, a cellular organelle that is essential for the Hh pathway, was impaired in mutant dermal condensate cells, suggesting that Gorab may be required for the Hh pathway through facilitating the formation of primary cilia. Thus, data obtained from this study provided insight into the biological functions of Gorab during embryonic morphogenesis of the skin in which Hh signaling and primary cilia exert important functions.
GORAB是一种主要定位于高尔基体的高尔基体蛋白，它与小GTP酶发生物理相互作用。GORAB在包括皮肤在内的哺乳动物组织中普遍表达。然而，这种高尔基体蛋白在皮肤中的生物学功能尚不清楚。在此，我们报告，破坏小鼠体内Gorab基因的表达会导致毛囊形态发生缺陷，其特征为毛囊角质形成细胞分化受损。这种毛囊表型与体内真皮凝聚物中刺猬信号通路（Hh）的显著抑制有关。Gorab缺陷的真皮间充质细胞在体外对Hh信号通路激活的反应能力也显著降低。此外，我们发现，作为Hh信号通路所必需的细胞器，初级纤毛的形成在突变的真皮凝聚细胞中受损，这表明Gorab可能通过促进初级纤毛的形成而参与Hh信号通路。因此，本研究获得的数据为深入了解Gorab在皮肤胚胎形态发生过程中的生物学功能提供了线索，其中Hh信号和初级纤毛发挥着重要作用。
