BICC1与PKD1和PKD2相互作用,在ADPKD中驱动细胞形成
Uyen Tran1, Andrew J Streets2, Devon Smith2
1Department of Heart, Blood & Kidney Research, Cleveland Clinic Research, Cleveland Clinic, Cleveland, United States.
eLife
|February 12, 2026
概括
比克c1蛋白与Polycystin-1和-2相互作用,这些蛋白与自身主导的多囊性病 (ADPKD) 相关. BICC1的变异可以加剧ADPKD的严重程度,这表明RNA代谢在疾病修饰中的作用.
科学领域:
- 遗传学 遗传学是一种遗传学.
- 分子生物学分子生物学
- 腎臟病學 (nephrology) 是一種醫學.
背景情况:
- 自体主导多囊性病 (ADPKD) 通常在成年期出现,由PKD1或PKD2的突变引起.
- 然而,可变的疾病表现包括非常早期的表现,表明其他遗传因素可能会影响严重程度.
- RNA结合分子Bicc1与动物模型中的多囊病 (PKD) 病原体有关.
研究的目的:
- 研究ADPKD中BICC1,PKD1和PKD2之间的功能相互作用.
- 确定BICC1变异是否有助于疾病严重程度,特别是在非常早期发病的PKD (VEO-PKD) 中.
主要方法:
- 生物化学测定证实了BICC1与多素-1和-2.2的结合.
- 在Xenopus和Bicc1枯竭的小鼠模型中进行功能丧失研究.
- 对大量ADPKD队列的基因分析,包括VEO-PKD患者.
- 基因组编辑以评估BICC1变异的影响.
主要成果:
- BICC1通过不同的蛋白质域与Polycystin-1和Polycystin-2进行物理相互作用.
- 在小鼠和Xenopus模型中,Bicc1的枯竭会加剧PKD,特别是当与Pkd1或Pkd2的损失相结合时.
- 在一对兄弟姐妹中发现了同卵性BICC1变体,在VEO-PKD患者中发现了复合异卵性BICC1变体.
- BICC1变异被证明是低形态的,并影响疾病相关的信号通路.
结论:
- 在脏发育和功能方面,BICC1与PKD1和PKD2功能合作.
- BICC1变种可以加剧ADPKD的严重程度,导致早期发病.
- RNA代谢代表了修改ADPKD进展的新疗法标.
相关概念视频
01:37Energy to Drive Translocation
2.9K
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...
2.9K
02:15M-Cdk Drives Transition Into Mitosis
6.6K
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
6.6K
01:27Drive-Reduction Theory: Push Theory of Motivation
1.3K
Clark Hull's drive-reduction theory, introduced in the 1940s and 1950s and often termed the "push theory" of motivation, provides a framework for understanding how biological and learned drives influence behavior. Hull suggested that motivation originates from the need to alleviate physiological tension caused by unmet biological necessities. The theory proposes that when a basic need, such as hunger or sleep, goes unfulfilled, it creates an internal imbalance. This imbalance, or...
1.3K
02:39Predator-Prey Interactions
21.7K
Predators consume prey for energy. Predators that acquire prey and prey that avoid predation both increase their chances of survival and reproduction (i.e., fitness). Routine predator-prey interactions elicit mutual adaptations that improve predator offenses, such as claws, teeth, and speed, as well as prey defenses, including crypsis, aposematism, and mimicry. Thus, predator-prey interactions resemble an evolutionary arms race.
21.7K
01:24Van der Waals Interactions
71.9K
Atoms and molecules interact with each other through intermolecular forces. These electrostatic forces arise from attractive or repulsive interactions between particles with permanent, partial, or temporary charges. The intermolecular forces between neutral atoms and molecules are ion–dipole, dipole–dipole, and dispersion forces, collectively known as van der Waals forces.
71.9K
02:57piRNA - Piwi-interacting RNAs
7.7K
PIWI-interacting RNAs, or piRNAs, are the most abundant short non-coding RNAs. More than 20,000 genes have been found in humans that code for piRNAs while only 2000 genes have been found for miRNAs. piRNAs can act at the transcriptional and post-transcriptional levels and have a vital role in silencing transposable elements present in germ cells. They are also involved in epigenetic silencing and activation. Previously, they were thought to function only in germ cells but new evidence suggests...
7.7K