ArticleThe Journal of biological chemistry2011
A single amino acid residue constitutes the third dimerization domain essential for the assembly and function of the tetrameric polycystin-2 (TRPP2) channel.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Designing genome editing experiments with EditABLE.Genome biology · 2026Article
- Article
- Identification of polycystin 2 missense mutants targeted for endoplasmic reticulum-associated degradation.American journal of physiology. Cell physiology · 2025Article
- Disease-associated missense mutations in the pore loop of polycystin-2 alter its ion channel function in a heterologous expression system.The Journal of biological chemistry · 2024Article
- UsingGenes · 2021Review
- A Novel Role for Polycystin-2 (Pkd2) inGenes · 2019Article
- Extracellular Loops Are Essential for the Assembly and Function of Polycystin Receptor-Ion Channel Complexes.The Journal of biological chemistry · 2017Article
- Regulation of TRPP3 Channel Function by N-terminal Domain Palmitoylation and Phosphorylation.The Journal of biological chemistry · 2016Article
- Conformational dynamics of Ca2+-dependent responses in the polycystin-2 C-terminal tail.The Biochemical journal · 2016Article
- A polycystin-centric view of cyst formation and disease: the polycystins revisited.Kidney international · 2015Review
- Vasopressin and disruption of calcium signalling in polycystic kidney disease.Nature reviews. Nephrology · 2015Review
- Oligomerization of the polycystin-2 C-terminal tail and effects on its Ca2+-binding properties.The Journal of biological chemistry · 2015Article
- A novel PKD2L1 C-terminal domain critical for trimerization and channel function.Scientific reports · 2015Article
- Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney disease.The Journal of clinical investigation · 2014Review
- New treatments for autosomal dominant polycystic kidney disease.British journal of clinical pharmacology · 2013Review
- Hyperphosphorylation of polycystin-2 at a critical residue in disease reveals an essential role for polycystin-1-regulated dephosphorylation.Human molecular genetics · 2013Article
- Human skeletal dysplasia caused by a constitutive activated transient receptor potential vanilloid 4 (TRPV4) cation channel mutation.Experimental & molecular medicine · 2012Review
- Ion channels in renal disease.Chemical reviews · 2012Review
- Calcium-induced conformational changes in C-terminal tail of polycystin-2 are necessary for channel gating.The Journal of biological chemistry · 2012Article
- The Kv7.2/Kv7.3 heterotetramer assembles with a random subunit arrangement.The Journal of biological chemistry · 2012Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Autosomal dominant polycystic kidney disease (ADPKD), the most common inherited cause of kidney failure, is caused by mutations in either PKD1 (85%) or PKD2 (15%). The PKD2 protein, polycystin-2 (PC2 or TRPP2), is a member of the transient receptor potential (TRP) superfamily and functions as a nonselective calcium channel. PC2 has been found to form oligomers in native tissues, suggesting that similar to other TRP channels, it may form functional homo- or heterotetramers with other TRP subunits. We have recently demonstrated that the homodimerization of PC2 is mediated by both N-terminal and C-terminal domains, and it is known that PC2 can heterodimerize with PC1, TRPC1, and TRPV4. In this paper, we report that a single cysteine residue, Cys(632), mutated in a known PKD2 pedigree, constitutes the third dimerization domain for PC2. PC2 truncation mutants lacking both N and C termini could still dimerize under nonreducing conditions. Mutation of Cys(632) alone abolished dimerization in these mutants, indicating that it was the critical residue mediating disulfide bond formation between PC2 monomers. Co-expression of C632A PC2 mutants with wild-type PC2 channels reduced ATP-sensitive endoplasmic reticulum Ca(2+) release in HEK293 cells. The combination of C632A and mutations disrupting the C-terminal coiled-coil domain (Val(846), Ile(853), Ile(860), Leu(867) or 4M) nearly abolished dimer formation and ATP-dependent Ca(2+) release. However, unlike the 4M PC2 mutant, a C632A mutant could still heterodimerize with polycystin-1 (PC1). Our results indicate that PC2 homodimerization is regulated by three distinct domains and that these events regulate formation of the tetrameric PC2 channel.
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