Megalin: from structure to function

doi:10.1038/s41581-026-01130-9

2026-09-18

PRE

Elynna B. Youm

Andrew Beenken

Ora A. Weisz

DOI：10.1038/s41581-026-01130-9

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摘要

En 中文

近端小管维持着一个强大的内吞通路，这对于从超滤液中回收蛋白质和维生素以及快速调节离子转运是必要的。多配体受体巨蛋白对于此过程至关重要。在巨蛋白功能缺失的情况下，通过内吞小室的膜和液体流动会受到严重损害，而巨蛋白与滤过药物的结合是肾毒性的主要原因。对巨蛋白结构的认识提供了关于巨蛋白如何通过pH依赖性构象重排驱动内吞动力学的线索，而聚焦离子束扫描电子显微镜和机器学习辅助分割的研究结果挑战了传统的近端小管内吞模型，转而支持一个模型，其中密集的顶膜小管网络（连同内质网）调控配体的通过、分裂和分离。除了作为内吞受体的功能外，巨蛋白还通过其他机制维持近端小管功能。基因组分析和动物研究显示，预测的巨蛋白表达改变对疾病进展和保护具有复杂影响。与这些观察结果一致，巨蛋白表达影响近端小管转录和细胞代谢，对疾病病理学产生重要后果。巨蛋白和杯蛋白是主要的内吞受体，它们结合并回收通过肾小球滤过屏障的蛋白质。本综述讨论了关于巨蛋白结构和近端小管内吞通路组织的理解进展，并探讨了巨蛋白在转录调控、代谢以及肾脏疾病易感性方面的新兴作用。

期刊

Nature Reviews Nephrology

IF:

39.8

论文数:

2.2K

被引数:

1.9W

机构

university of pittsburgh school of medicine

学者数:

175

论文数: 64

被引数: 0

Columbia University Vagelos College of Physicians and Surgeons

学者数:

论文数: 25

被引数: 0

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