Gp280/Intrinsic factor-vitamin B12 receptor/Cubilin (CUBN) is a large endocytic receptor serving multiple functions in vitamin B12 homeostasis, renal reabsorption of protein or toxic substances including albumin, vitamin D-binding protein or cadmium. Cubilin is a peripheral membrane protein consisting of 8 Epidermal Growth Factor (EGF)-like repeats and 27 CUB (defined as Complement C1r/C1s, Uegf, BMP1) domains. This structurally unique protein interacts with at least two molecular partners, Amnionless (AMN) and Lrp2/Megalin. AMN is involved in appropriate plasma membrane transport of Cubilin whereas Lrp2 is essential for efficient internalization of Cubilin and its ligands. Observations gleaned from animal models with Cubn deficiency or human diseases demonstrate the importance of this protein. In this review addressed to basic research and medical scientists, we summarize currently available data on Cubilin and its implication in renal and intestinal biology. We also discuss the role of Cubilin as a modulator of Fgf8 signaling during embryonic development and propose that the Cubilin-Fgf8 interaction may be relevant in human pathology, including in cancer progression, heart or neural tube defects. We finally provide experimental elements suggesting that some aspects of Cubilin physiology might be relevant in drug design.

中文翻译：

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Cubilin，发展和疾病中的内在因子-维生素B12受体。

Gp280 /内在因子维生素B12受体/ Cubilin（CUBN）是一种大型的内吞受体，在维生素B12稳态，肾脏对蛋白质或包括白蛋白，维生素D结合蛋白或镉的有毒物质的重吸收中具有多种功能。胆蛋白是一种外围膜蛋白，由8个表皮生长因子（EGF）样重复序列和27个CUB（定义为补体C1r / C1s，Uegf，BMP1）域组成。这种结构独特的蛋白质与至少两个分子伴侣相互作用，即Amnionless（AMN）和Lrp2 / Megalin。AMN参与了Cubilin的适当质膜运输，而Lrp2对于有效地使Cubilin及其配体内化至关重要。从具有Cubn缺乏症或人类疾病的动物模型中收集的观察结果证明了这种蛋白质的重要​​性。在这篇针对基础研究和医学科学家的综述中，我们总结了有关胆红素及其在肾脏和肠道生物学中的意义的现有数据。我们还讨论了脐带蛋白在胚胎发育过程中作为Fgf8信号调节剂的作用，并提出Cubilin-Fgf8相互作用可能与人类病理学相关，包括癌症进展，心脏或神经管缺陷。最后，我们提供了实验元素，表明Cubilin生理学的某些方面可能与药物设计有关。包括癌症进展，心脏或神经管缺陷。最后，我们提供了实验元素，这些结果暗示了Cubilin生理学的某些方面可能与药物设计有关。包括癌症进展，心脏或神经管缺陷。最后，我们提供了实验元素，这些结果暗示了Cubilin生理学的某些方面可能与药物设计有关。