Structural interaction and functional regulation of polycystin-2 by filamin.
Filamins are important actin cross-linking proteins implicated in scaffolding, membrane stabilization and signal transduction, through interaction with ion channels, receptors and signaling proteins. Here we report the physical and functional interaction between filamins and polycystin-2, a TRP-type...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3393660?pdf=render |
| _version_ | 1818529255698464768 |
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| author | Qian Wang Xiao-Qing Dai Qiang Li Zuocheng Wang María del Rocío Cantero Shu Li Ji Shen Jian-Cheng Tu Horacio Cantiello Xing-Zhen Chen |
| author_facet | Qian Wang Xiao-Qing Dai Qiang Li Zuocheng Wang María del Rocío Cantero Shu Li Ji Shen Jian-Cheng Tu Horacio Cantiello Xing-Zhen Chen |
| author_sort | Qian Wang |
| collection | DOAJ |
| description | Filamins are important actin cross-linking proteins implicated in scaffolding, membrane stabilization and signal transduction, through interaction with ion channels, receptors and signaling proteins. Here we report the physical and functional interaction between filamins and polycystin-2, a TRP-type cation channel mutated in 10-15% patients with autosomal dominant polycystic kidney disease. Yeast two-hybrid and GST pull-down experiments demonstrated that the C-termini of filamin isoforms A, B and C directly bind to both the intracellular N- and C-termini of polycystin-2. Reciprocal co-immunoprecipitation experiments showed that endogenous polycystin-2 and filamins are in the same complexes in renal epithelial cells and human melanoma A7 cells. We then examined the effect of filamin on polycystin-2 channel function by electrophysiology studies with a lipid bilayer reconstitution system and found that filamin-A substantially inhibits polycystin-2 channel activity. Our study indicates that filamins are important regulators of polycystin-2 channel function, and further links actin cytoskeletal dynamics to the regulation of this channel protein. |
| first_indexed | 2024-12-11T17:04:33Z |
| format | Article |
| id | doaj.art-06dfc2457bac472b9cf4cac8801dda12 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T17:04:33Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-06dfc2457bac472b9cf4cac8801dda122022-12-22T00:57:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0177e4044810.1371/journal.pone.0040448Structural interaction and functional regulation of polycystin-2 by filamin.Qian WangXiao-Qing DaiQiang LiZuocheng WangMaría del Rocío CanteroShu LiJi ShenJian-Cheng TuHoracio CantielloXing-Zhen ChenFilamins are important actin cross-linking proteins implicated in scaffolding, membrane stabilization and signal transduction, through interaction with ion channels, receptors and signaling proteins. Here we report the physical and functional interaction between filamins and polycystin-2, a TRP-type cation channel mutated in 10-15% patients with autosomal dominant polycystic kidney disease. Yeast two-hybrid and GST pull-down experiments demonstrated that the C-termini of filamin isoforms A, B and C directly bind to both the intracellular N- and C-termini of polycystin-2. Reciprocal co-immunoprecipitation experiments showed that endogenous polycystin-2 and filamins are in the same complexes in renal epithelial cells and human melanoma A7 cells. We then examined the effect of filamin on polycystin-2 channel function by electrophysiology studies with a lipid bilayer reconstitution system and found that filamin-A substantially inhibits polycystin-2 channel activity. Our study indicates that filamins are important regulators of polycystin-2 channel function, and further links actin cytoskeletal dynamics to the regulation of this channel protein.http://europepmc.org/articles/PMC3393660?pdf=render |
| spellingShingle | Qian Wang Xiao-Qing Dai Qiang Li Zuocheng Wang María del Rocío Cantero Shu Li Ji Shen Jian-Cheng Tu Horacio Cantiello Xing-Zhen Chen Structural interaction and functional regulation of polycystin-2 by filamin. PLoS ONE |
| title | Structural interaction and functional regulation of polycystin-2 by filamin. |
| title_full | Structural interaction and functional regulation of polycystin-2 by filamin. |
| title_fullStr | Structural interaction and functional regulation of polycystin-2 by filamin. |
| title_full_unstemmed | Structural interaction and functional regulation of polycystin-2 by filamin. |
| title_short | Structural interaction and functional regulation of polycystin-2 by filamin. |
| title_sort | structural interaction and functional regulation of polycystin 2 by filamin |
| url | http://europepmc.org/articles/PMC3393660?pdf=render |
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