RSPO1,即R-spondin 1,是一种由成纤维细胞分泌的蛋白质,属于R-spondin蛋白家族。这个家族的成员在生殖器官发育、上皮干细胞更新以及癌症诱导或抑制等方面发挥着重要作用。RSPO1基因的突变会导致多种疾病,如掌跖角化症伴皮肤鳞状细胞癌、46XX性反转和真两性畸形。RSPO1基因编码的蛋白质能够激活经典的β-catenin信号通路,这对于女性体细胞分化和生殖细胞向减数分裂的承诺至关重要。
RSPO1蛋白在多种生物学过程中发挥着关键作用。例如,RSPO1可以激活LGR4-Wnt/β-catenin信号通路,抑制脂肪细胞的线粒体呼吸和产热,从而促进肥胖的发生[1]。在肝脏中,RSPO1蛋白可以标记活跃分裂的干细胞,并促进这些细胞的克隆扩增和分化[2]。此外,RSPO1蛋白还可以激活TGF-β信号通路,并促进成纤维细胞的增殖和侵袭[3]。
RSPO1蛋白在性别决定中也发挥着重要作用。在哺乳动物中,胚胎的性别是由其是否表达Sry和Sox9基因来决定的。如果胚胎表达Sry和Sox9基因,就会发育成雄性;如果不表达,就会发育成雌性。RSPO1基因的突变可以导致女性向男性的性反转[4][7]。此外,在非哺乳动物中,如鱼类,RSPO1蛋白的过表达可以诱导XY性别的个体发育成雌性[5]。
RSPO1蛋白还可以调节神经嵴细胞的形成。神经嵴细胞是发育过程中产生多种细胞类型的细胞,包括神经元、皮肤细胞和色素细胞等。RSPO1和Wnt蛋白在神经管发育的早期阶段共同表达,并协同调节神经嵴细胞的形成[6]。
总之,RSPO1蛋白是一种多功能的蛋白质,在多种生物学过程中发挥着重要作用。RSPO1蛋白的异常表达或功能缺失可能导致多种疾病的发生,如肥胖、癌症和性发育异常等。因此,深入研究RSPO1蛋白的功能和作用机制对于理解这些疾病的发病机制和开发新的治疗方法具有重要意义。
参考文献:
1. Sun, Yingkai, Zhang, Juan, Hong, Jie, Liu, Ruixin, Wang, Jiqiu. 2023. Human RSPO1 Mutation Represses Beige Adipocyte Thermogenesis and Contributes to Diet-Induced Adiposity. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 10, e2207152. doi:10.1002/advs.202207152. https://pubmed.ncbi.nlm.nih.gov/36755192/
2. Huch, Meritxell, Dorrell, Craig, Boj, Sylvia F, Grompe, Markus, Clevers, Hans. 2013. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. In Nature, 494, 247-50. doi:10.1038/nature11826. https://pubmed.ncbi.nlm.nih.gov/23354049/
3. Dellambra, Elena, Cordisco, Sonia, Proto, Vittoria, Castiglia, Daniele, Guerra, Liliana. . RSPO1-mutated fibroblasts from non-tumoural areas of palmoplantar keratoderma display a cancer-associated phenotype. In European journal of dermatology : EJD, 31, 342-350. doi:10.1684/ejd.2021.4066. https://pubmed.ncbi.nlm.nih.gov/34309520/
4. Chassot, A A, Gregoire, E P, Magliano, M, Lavery, R, Chaboissier, M C. 2008. Genetics of ovarian differentiation: Rspo1, a major player. In Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation, 2, 219-27. doi:10.1159/000152038. https://pubmed.ncbi.nlm.nih.gov/18987496/
5. Zhou, Linyan, Charkraborty, Tapas, Zhou, Qian, Nagahama, Yoshitaka, Zhang, Yueguang. 2016. Rspo1-activated signalling molecules are sufficient to induce ovarian differentiation in XY medaka (Oryzias latipes). In Scientific reports, 6, 19543. doi:10.1038/srep19543. https://pubmed.ncbi.nlm.nih.gov/26782368/
6. Shinozuka, Takuma, Aoki, Motoko, Hatakeyama, Yudai, Okamoto, Hitoshi, Takada, Shinji. 2023. Rspo1 and Rspo3 are required for sensory lineage neural crest formation in mouse embryos. In Developmental dynamics : an official publication of the American Association of Anatomists, 253, 435-446. doi:10.1002/dvdy.659. https://pubmed.ncbi.nlm.nih.gov/37767857/
7. Tallapaka, Karthik, Venugopal, Vineeth, Dalal, Ashwin, Aggarwal, Shagun. . Novel RSPO1 mutation causing 46,XX testicular disorder of sex development with palmoplantar keratoderma: A review of literature and expansion of clinical phenotype. In American journal of medical genetics. Part A, 176, 1006-1010. doi:10.1002/ajmg.a.38646. https://pubmed.ncbi.nlm.nih.gov/29575617/