Folate Receptors and Therapeutic Applications
Folate Receptors and Therapeutic Applications
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DOI：
10.1007/978-1-4419-8417-3_2
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Kamen, Barton A.
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文献类型：
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作者：
Kamen, Barton A.
叶酸受体（FRs）是由位于11号染色体11q13端粒上的基因编码的一个蛋白家族。现在有四个成员：alpha， beta， gamma和delta。前两种亚型是研究得最好的，它们是药理学和免疫疗法的靶点。关于叶酸体内平衡的后两种亚型，我们所知甚少。前两种都是糖基磷脂酰肌醇连接蛋白，尽管血浆和牛奶中也存在可溶性形式。FR α在许多癌症中过度表达。它是被研究得最彻底的同工异构体，它一直是受体介导的叶酸摄取的模型，这一过程被称为“胞血症”。为了通过上皮介导叶酸摄取或胞吞作用，FR似乎与最近描述的质子偶联叶酸转运蛋白（PCFT）协同工作。FR β在活化的巨噬细胞上表达，它是治疗自身免疫性疾病患者的靶标。本文就其功能及其在细胞膜脂筏中的循环调控作一综述。异常、缺失或可溶性FR水平及相关自身抗体的临床意义也将在胚胎病和神经认知功能障碍的基础上进行讨论。
The folate receptors (FRs) are a family of proteins coded by genes located on chromosome 11 at 11q13 telomeric to Cyclin DI. There are now four members: alpha, beta, gamma, and delta. The first two isoforms are the best studied, and they are targets for both pharmacological and immunotherapies. There is little known about the last two isoforms relative to folate homeostasis. The first two are both glycosylphosphatidylinositol-linked proteins, although soluble forms in plasma and milk also exist. FR alpha is overexpressed by many carcinomas. It is the most completely studied isoform, and it has been the model for receptor-mediated folate uptake by a process named "potocytosis." To mediate folate uptake or transcytosis through epithelia, the FR appears to work in tandem with the recently described proton-coupled folate transporter (PCFT). FR beta is expressed on activated macrophages, and it is being targeted for therapy of patients with autoimmune diseases. The function of the FR, as well as regulation of its cycling in the lipid rafts on the cell membrane, is the subject of this review. The clinical significance of abnormal, missing, or soluble FR levels and associated autoantibodies will also be discussed in light of embryopathies and neurocognitive dysfunction.