The Gating of Polycystin Signaling Complex
Mutations in either polycystin-2 (PC2) or polycystin-1 (PC1) proteins cause severe, potentially lethal, kidney disorders (autosomal dominant polycystic kidney disease, ADPKD) and multiple extrarenal disease phenotypes. PC2, a member of the transient receptor potential channel superfamily and PC1, an...
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doaj-3a45db3cce5440ba88d31660858ecc272020-11-24T21:00:18ZengBMCBiological Research0716-97600717-62872004-01-01374681691The Gating of Polycystin Signaling ComplexPATRICK DELMASMutations in either polycystin-2 (PC2) or polycystin-1 (PC1) proteins cause severe, potentially lethal, kidney disorders (autosomal dominant polycystic kidney disease, ADPKD) and multiple extrarenal disease phenotypes. PC2, a member of the transient receptor potential channel superfamily and PC1, an orphan membrane receptor of largely unknown function, are thought to be part of a common signalling pathway. Here, I show that co-assembly of full-length PC1 with PC2 forms an ion channel signalling complex in which PC1 regulates PC2 channel gating through a structural rearrangement of the polycystin complex (Delmas et al., 2004a). These polycystin complexes function either as a receptor-cation channel or as a G-protein-coupled receptor. Thus, PC1 acts as a prototypical membrane receptor that regulates G-proteins and plasmalemmal PC2, a bimodal mechanism that may account for the multifunctional roles of polycystin proteins in various cell types. Genetic alteration of polycystin proteins such as those occurring in kidney diseases may impede polycystin signalling, thereby providing a likely mechanistic explanation to the pathogenesis of ADPKD. Our proposed mechanism may also be paradigmatic for the function of polycystin orthologues and other polycystin-related proteins in a variety of nonrenal cell types, including sperm, muscle cells and sensory neuronshttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400026PolycystinTRP channelSensory transductionCalcium signalingPolycystic Kidney Disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
PATRICK DELMAS |
spellingShingle |
PATRICK DELMAS The Gating of Polycystin Signaling Complex Biological Research Polycystin TRP channel Sensory transduction Calcium signaling Polycystic Kidney Disease |
author_facet |
PATRICK DELMAS |
author_sort |
PATRICK DELMAS |
title |
The Gating of Polycystin Signaling Complex |
title_short |
The Gating of Polycystin Signaling Complex |
title_full |
The Gating of Polycystin Signaling Complex |
title_fullStr |
The Gating of Polycystin Signaling Complex |
title_full_unstemmed |
The Gating of Polycystin Signaling Complex |
title_sort |
gating of polycystin signaling complex |
publisher |
BMC |
series |
Biological Research |
issn |
0716-9760 0717-6287 |
publishDate |
2004-01-01 |
description |
Mutations in either polycystin-2 (PC2) or polycystin-1 (PC1) proteins cause severe, potentially lethal, kidney disorders (autosomal dominant polycystic kidney disease, ADPKD) and multiple extrarenal disease phenotypes. PC2, a member of the transient receptor potential channel superfamily and PC1, an orphan membrane receptor of largely unknown function, are thought to be part of a common signalling pathway. Here, I show that co-assembly of full-length PC1 with PC2 forms an ion channel signalling complex in which PC1 regulates PC2 channel gating through a structural rearrangement of the polycystin complex (Delmas et al., 2004a). These polycystin complexes function either as a receptor-cation channel or as a G-protein-coupled receptor. Thus, PC1 acts as a prototypical membrane receptor that regulates G-proteins and plasmalemmal PC2, a bimodal mechanism that may account for the multifunctional roles of polycystin proteins in various cell types. Genetic alteration of polycystin proteins such as those occurring in kidney diseases may impede polycystin signalling, thereby providing a likely mechanistic explanation to the pathogenesis of ADPKD. Our proposed mechanism may also be paradigmatic for the function of polycystin orthologues and other polycystin-related proteins in a variety of nonrenal cell types, including sperm, muscle cells and sensory neurons |
topic |
Polycystin TRP channel Sensory transduction Calcium signaling Polycystic Kidney Disease |
url |
http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602004000400026 |
work_keys_str_mv |
AT patrickdelmas thegatingofpolycystinsignalingcomplex AT patrickdelmas gatingofpolycystinsignalingcomplex |
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1716780222432411648 |