Related Experiment Video
Updated: Jun 16, 2026
10:05
In Vitro Analysis of PDZ-dependent CFTR Macromolecular Signaling Complexes
Published on: August 13, 2012
A polycystin-2 (TRPP2) dimerization domain essential for the function of heteromeric polycystin complexes
Aurélie Giamarchi1, Shuang Feng, Lise Rodat-Despoix
1Centre de Recherche en Neurophysiologie et Neurobiologie de Marseille, UMR 6231, CNRS, Université de la Méditerranée, Bd Pierre Dramard, Marseille Cedex 15, France.
The EMBO Journal
|February 20, 2010
Summary
Autosomal dominant polycystic kidney disease (ADPKD) arises from mutations in PKD1 and PKD2. A C-terminal domain in PC2 is crucial for PC1/PC2 complex formation, impacting kidney cyst development.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder caused by mutations in PKD1 and PKD2 genes.
- Polycystin-1 (PC1) and Polycystin-2 (PC2) proteins form complexes essential for kidney development.
- The precise molecular mechanisms governing polycystin complex assembly and function remain incompletely understood.
Purpose of the Study:
- To investigate the role of the C-terminus of PC2 in polycystin complex formation and function.
- To determine whether PC2 self-oligomerization is required for PC1/PC2 complex assembly.
- To elucidate the molecular basis of cyst formation in ADPKD related to PC2 function.
Main Methods:
- Identification and characterization of a coiled-coil homodimerization domain in the C-terminus of PC2.
- Generation and analysis of dimerization-defective PC2 mutants.
- Assessment of PC1/PC2 complex formation at cellular compartments (plasma membrane, ER junctions).
- Functional assays of PC2 as an ER Ca(2+) channel.
- In vivo studies using zebrafish models to evaluate the effects of PC2 mutants on organogenesis and laterality.
Main Results:
- A C-terminal coiled-coil domain in PC2 was identified as essential for PC1 binding and PC1/PC2 complex formation.
- Dimerization-defective PC2 mutants failed to form PC1/PC2 complexes at the plasma membrane and ER junctions.
- These mutants retained function as ER Ca(2+) release channels.
- Expression of dimerization-defective PC2 in zebrafish led to a cystic kidney phenotype with minimal effects on organ laterality.
Conclusions:
- C-terminal dimerization of PC2 is critical for specifying the assembly of functional PC1/PC2 complexes.
- PC2 dimerization is not required for its function as an ER Ca(2+) channel.
- Disruptions in PC2 homo- and heteromerization are implicated as the molecular cause of cystogenesis in ADPKD.
More Related Videos
08:27Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy
Published on: January 7, 2019
10:20Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b
Published on: November 11, 2016
Related Concept Videos
01:20Cotranslational Protein Translocation
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
01:28Protein Translocation Machinery on the ER Membrane
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the translocon complex.
01:29Insertion of Multi-pass Transmembrane Proteins in the RER
The rough ER membrane synthesizes, assembles, and embeds transmembrane proteins in diverse topologies. These proteins function as transporters or channels and can remain in the ER membrane or are sent to the Golgi complex, lysosome, and cell membrane.
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...
01:30Assembly of Signaling Complexes
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
01:09Cytoskeletal Linker Proteins - Plakins
Plakins are large proteins with binding domains for microtubules, microfilaments, intermediate filaments, and membrane-associated protein complexes at cell junctions. Plakin functions are evolutionarily conserved and are primarily involved in organizing the different components of the cytoskeleton by crosslinking them to each other and connecting them to the cell-matrix and cell adhesion complexes. They are also known to interact with signal transducers, serve as scaffolds for signaling...
02:18Intrinsically Disordered Proteins
Intrinsically disordered proteins are a group of proteins that do not fold into specific three-dimensional structures. Their structural flexibility allows them to complement ordered proteins to perform functions that are inaccessible to rigid structures. They are more common in eukaryotes than prokaryotes and may either be exclusively intrinsically disordered or hybrid proteins, consisting of a mix of ordered and disordered regions. The absence of a rigid structure in these proteins can be...