Van Gorp Hanne, Kuchmiy Anna, Van Hauwermeiren Filip, Lamkanfi Mohamed
Department of Medical Protein Research, VIB, Ghent, Belgium; Department of Biochemistry, Ghent University, Ghent, Belgium.
FEBS J. 2014 Oct;281(20):4568-82. doi: 10.1111/febs.13014. Epub 2014 Sep 30.
Nucleotide-binding oligomerization domain receptors (NOD-like receptors, NLRs) are intracellular proteins that are chiefly known for their critical functions in inflammatory responses and host defense against microbial pathogens. Several NLRs have been demonstrated to assemble inflammasomes or to engage transcriptional signaling cascades that result in the production of pro-inflammatory cytokines and bactericidal factors. In recent years, NLRs have also emerged as key regulators of early mammalian embryogenesis and reproduction. A subset of phylogenetically related NLRs represents a new class of maternal effect genes that are highly expressed in maturing oocytes and pre-implantation embryos. Mutations in several of these NLRs have been linked to hereditary reproductive defects and imprinting diseases. In this review, we discuss the expression profiles, the emerging functions and molecular mode of action of these NLRs with newly recognized roles at the interfaces of the immune and reproductive systems. In addition, we provide an overview of coding mutations in NLRs that have been associated with human reproductive diseases, and outline crucial outstanding questions in this emerging research field.
核苷酸结合寡聚化结构域受体（NOD样受体，NLRs）是细胞内蛋白质，主要因其在炎症反应和宿主抵御微生物病原体中的关键功能而闻名。已证实几种NLRs可组装炎性小体或参与转录信号级联反应，从而导致促炎细胞因子和杀菌因子的产生。近年来，NLRs也已成为早期哺乳动物胚胎发生和生殖的关键调节因子。一组系统发育相关的NLRs代表了一类新的母体效应基因，在成熟卵母细胞和植入前胚胎中高度表达。其中几种NLRs的突变与遗传性生殖缺陷和印记疾病有关。在本综述中，我们讨论了这些NLRs的表达谱、新出现的功能和分子作用模式，它们在免疫和生殖系统的界面上具有新认识的作用。此外，我们概述了与人类生殖疾病相关的NLRs编码突变，并概述了这一新兴研究领域中至关重要的悬而未决的问题。
