The RAIG family member, GPRC5D, is associated with hard-keratinized structures
The RAIG family member, GPRC5D, is associated with hard-keratinized structures
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DOI：
10.1046/j.0022-202x.2004.12628.x
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发表时间：
2004-03-01
影响因子：
6.5
通讯作者：
Shimomura, T
中科院分区：
文献类型：
--
作者：
Inoue, S;Nambu, T;Shimomura, T
维甲酸诱导基因-1最初被鉴定为维甲酸诱导的孤儿G蛋白偶联受体。三个高度同源的oGPCR(GPRC5B、GPRC5C和GPRC5D)被归类为RAIG1家族。我们在这里描述了GPRC5D独特的组织分布及其表达机制。原位杂交表明，GPRC5D表达于产生硬角蛋白的分化细胞，包括毛干的皮质细胞、指甲的角质区和舌丝状乳头的中央区域。GPRC5D转录本在生长期中期和晚期的毛囊和退化期的毛囊中表达，但在末期和生长期早期不表达。分化诱导剂全反式维甲酸诱导培养的毛球细胞表达GPRC5D。由于GPRC5D的组织分布与构成硬上皮组织主要结构蛋白的硬角蛋白有关，因此我们研究了GPRC5D对酸性硬角蛋白的影响。对培养细胞的分析表明，瞬时过表达导致HA3的抑制和HA4发角蛋白基因的表达。该基因在WHN缺失(裸)小鼠的毛囊中保持表达，表明该基因受到不同于毛发角蛋白合成的信号途径的调控。总之，这些数据为理解GPRC5D在硬角化中作用的分子机制提供了一个框架。
Retinoic acid-inducible gene-1 was originally identified as an orphan G-protein coupled receptor induced by retinoic acid. Three highly homologous oGPCR (GPRC5B, GPRC5C, and GPRC5D) have since been classified into the RAIG1 family. We describe here, the unique tissue distribution of GPRC5D and its mechanism of expression. Hybridization in situ has shown that GPRC5D is expressed in differentiating cells that produce hard keratin, including cortical cells of the hair shaft, the keratogenous zone of the nail, and in a central region of the filiform papillae of the tongue. The GPRC5D transcript is expressed in hair follicles during mid- and late anagen, and catagen but not at telogen and early anagen phases. The differentiation-inducer, all-trans retinoic acid, induces GPRC5D expression in cultured hair bulb cells. Because the tissue distribution of GPRC5D indicates a relationship with hard keratins that constitute the major structural proteins of hard epithelial tissues, we investigated the effect of GPRC5D on acid hard keratins. Analyses of cultured cells showed that transient overexpression resulted in suppression of Ha3 and stimulation of Ha4 hair keratin gene expression. The expression was maintained in the hair follicles of whn-deficient (nude) mice, suggesting that this gene is regulated by a signal pathway different from that of hair keratin synthesis. Collectively, these data provide a framework for understanding the molecular mechanisms of GPRC5D function in hard keratinization.