Related Experiment Video
Updated: Apr 18, 2026
08:46
Implementing Patch Clamp and Live Fluorescence Microscopy to Monitor Functional Properties of Freshly Isolated PKD Epithelium
Published on: September 1, 2015
10.3K
Polycystin-1 maturation requires polycystin-2 in a dose-dependent manner
The Journal of Clinical Investigation
|January 10, 2015
Summary
Polycystin-2 (PC2) acts as a chaperone, essential for the maturation and surface localization of polycystin-1 (PC1). Reduced PC2 levels impair PC1 maturation, impacting disease severity in autosomal dominant polycystic kidney disease (ADPKD).
Area of Science:
- Nephrology
- Molecular Biology
- Genetics
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited kidney disorder caused by mutations in PKD1 or PKD2 genes.
- Mutations in PKD1 are linked to more severe renal disease, and disease severity correlates with the mature polycystin-1 (PC1) glycoform levels.
- Polycystin-1 (PC1) and polycystin-2 (PC2) form a complex, but the precise role of PC2 in PC1 maturation and disease pathogenesis remains unclear.
Purpose of the Study:
- To elucidate the role of PC2 in PC1 maturation and surface localization.
- To investigate how PC2's chaperone function affects PC1 processing and ADPKD severity.
- To determine the relationship between PC1 and PC2 levels and their combined impact on kidney disease progression.
Main Methods:
- Utilized mouse models with varying Pkd1 and Pkd2 gene mutations (Pkd2-/-, Pkd2 heterozygotes).
- Examined PC1 and PC2 interaction in the endoplasmic reticulum (ER) and subsequent PC1 cleavage.
- Assessed PC1 maturation, glycoform levels, and surface localization in relation to PC2 levels and function.
Main Results:
- PC1 and PC2 first interact in the ER prior to PC1 cleavage at the GPS/GAIN site.
- PC2 functions as a crucial chaperone for PC1 maturation and surface expression, dependent on its distal coiled-coil domain.
- Complete loss of PC2 (Pkd2-/-) prevented PC1 maturation, while partial reduction (heterozygotes) led to a significant decrease in mature PC1 glycoform.
- Reduced levels of functional PC1 and PC2 in kidneys of interbred models resulted in severe, rapidly progressive polycystic kidney disease.
Conclusions:
- PC2 is essential for the proper maturation and trafficking of PC1.
- The chaperone activity of PC2 directly influences the levels of mature PC1.
- Mature PC1 levels are a critical determinant of disease severity in both PKD1 and PKD2, highlighting the importance of PC1-PC2 complex function.
More Related Videos
12:47Spectral Karyotyping to Study Chromosome Abnormalities in Humans and Mice with Polycystic Kidney Disease
Published on: February 3, 2012
39.5K
07:35Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring
Published on: June 23, 2015
12.1K
Related Concept Videos
01:26Bacterial Protein Maturation
737
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
737
02:02Meiosis II
52.1K
Meiosis II entails cell division and segregation of the sister chromatids, resulting in the production of four unique haploid gametes. The steps for meiosis II are similar to mitosis, except that meiosis II occurs in haploid cells, whereas mitosis occurs in diploid cells.
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
The timing and cell division patterns of meiosis differ between males and females. In male meiosis, the centrosomes are part of the formation of the meiotic spindle. However, in oocytes, including that of humans, Drosophila,...
52.1K
01:26Transport Across the Golgi
6.8K
While it is unclear how molecules move between adjacent Golgi cisternae, it is apparent that the molecules move from cis- cisterna, the entry face, to the trans- cisterna, the exit face. Experiments initially suggested vesicles that bud from one cisterna and fuse with the next cisterna to transport proteins between the cisternae. This vesicular transport model describes the Golgi apparatus as a relatively static structure with a unique enzyme composition in each cisterna. Molecules are...
6.8K
02:23Abnormal Proliferation
5.5K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.5K
00:50Anaphase Promoting Complex
3.6K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.6K
01:45Positive Regulator Molecules
137.4K
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
137.4K