Cell. 2009 Oct 30;139(3):587-96.
Polycystin-1 and -2 dosage regulates pressure sensing.
Sharif-Naeini, R., Folgering, J. H., Bichet, D., Duprat, F., Lauritzen, I., Arhatte, M., Jodar, M., Dedman, A., Chatelain, F. C., Schulte, U., Retailleau, K., Loufrani, L., Patel, A., Sachs, F., Delmas, P., Peters, D. J., Honore, E.,
["Institut de Pharmacologie Moleculaire et Cellulaire, UMR CNRS 6097, Universite de Nice Sophia Antipolis, 06560 Valbonne, France."]
["Institut de Pharmacologie Moleculaire et Cellulaire, UMR CNRS 6097, Universite de Nice Sophia Antipolis, 06560 Valbonne, France."]
Autosomal-dominant polycystic kidney disease, the most frequent monogenic cause of kidney failure, is induced by mutations in the PKD1 or PKD2 genes, encoding polycystins TRPP1 and TRPP2, respectively. Polycystins are proposed to form a flow-sensitive ion channel complex in the primary cilium of both epithelial and endothelial cells. However, how polycystins contribute to cellular mechanosensitivity remains obscure. Here, we show that TRPP2 inhibits stretch-activated ion channels (SACs). This specific effect is reversed by coexpression with TRPP1, indicating that the TRPP1/TRPP2 ratio regulates pressure sensing. Moreover, deletion of TRPP1 in smooth muscle cells reduces SAC activity and the arterial myogenic tone. Inversely, depletion of TRPP2 in TRPP1-deficient arteries rescues both SAC opening and the myogenic response. Finally, we show that TRPP2 interacts with filamin A and demonstrate that this actin crosslinking protein is critical for SAC regulation. This work uncovers a role for polycystins in regulating pressure sensing.
PMID: 19879844
 Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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Screening
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| Experimental screening | Non-experimental screening | Reference | ||||||||
| TRP channel construct | Interactor source | |||||||||
| TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
| TRPP1 |
|
ABHD12 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
ATP13A1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
BAG2 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
BRI3BP | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
Calnexin | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
CDKAL1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
CISD2 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
Cullin-1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
DHRS7B | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
DNAJA1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
EPHA2 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
ERLIN2 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
FAF2 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
Filamin-A | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
H2-D1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
H2-K1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
IFIT1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
IP3R1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
IP3R3 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
KRAS | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
LAP2/TMPO | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
LETMD1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
MGST1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
Numb | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
Nup155 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
p97/VCP | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
Paraoxonase 3 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
PDIA3/GRP58 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
PGAM5 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
PKD1/Polycystin-1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
PTP1B | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
RAB12 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
RAB14 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
RAB18 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
RAB21 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
RAB7 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
RAD50 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
RCHY1/PIRH2 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
Ribophorin I | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
Ribophorin II | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
RTP4 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
SEC22B | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
SEC61B | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
SERCA2 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
SGPL1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
SKP1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
SRPRB | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
SSFA2 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
ST7 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
SUN3 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
TAP1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
TAP2 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
Tapasin | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
TBL2 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
TFRC | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
TMEM120a | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
TMEM209 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
TMEM48/NDC1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
TMEM59 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
TOR1AIP1/LAB1B | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
TRIM59 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
TTC35 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
TYW1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
UHRF1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
USE1 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
VAMPA | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
VAMPB | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
VDAC3 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
Viperin | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
VRK2 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
VTI1B | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
| TRPP1 |
|
β-Trcp2 | Affinity purification-mass spectrometry | Mouse | Not specified | Mouse | Vascular smooth muscle | MOVAS lysates | 19879844 | |
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
|
Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
|
top
|
| Validation: In vivo validation
|
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
| Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPP1 |
|
Filamin-A | Co-immunoprecipitation | COS-7 | 19879844 | |||||
(:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)