Cell. 2009 Oct 30;139(3):587-96. doi: 10.1016/j.cell.2009.08.045.

Polycystin-1 and -2 dosage regulates pressure sensing.External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c

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."]
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: 19879844External 2231691f894ba696de1310221b0a0dbbb31a7251e75115c265587c3d9d5f507c
Screening Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  Experimental screening Non-experimental screening Reference
TRP channel construct Interactor source
TRP channel Interactor Method Species Region Species Organ/tissue Sample type
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 ABHD12 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 ATP13A1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 BAG2 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 BRI3BP Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Calnexin Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 CDKAL1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 CISD2 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Cullin-1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 DHRS7B Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 EPHA2 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 ERLIN2 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 FAF2 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Filamin-A Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Ƣ-Trcp2 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 H2-D1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 H2-K1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 HSP40/DNAJA1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IFIT1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 IP3R3 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 KRAS Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 LAP2/TMPO Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 LETMD1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 MGST1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Numb Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Nup155 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 p97/VCP Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Paraoxonase 3 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PDIA3/GRP58 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PGAM5 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PKD1/Polycystin-1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 PTP1B Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 RAB12 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 RAB14 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 RAB18 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 RAB21 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 RAB7 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 RAD50 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 RCHY1/PIRH2 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Ribophorin I Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Ribophorin II Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 RTP4 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 SEC22B Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 SEC61B Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 SERCA2 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 SGPL1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 SKP1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 SRPRB Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 SSFA2 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 ST7 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 SUN3 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TAP1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TAP2 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Tapasin Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TBL2 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TFRC Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TMEM120a Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TMEM209 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TMEM48/NDC1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TMEM59 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TOR1AIP1/LAB1B Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TRIM59 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TTC35 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 TYW1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 UHRF1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 USE1 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 VAMPA Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 VAMPB Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 VDAC3 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Viperin Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 VRK2 Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
TRPP1 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 VTI1B Affinity purification-mass spectrometry Mouse Not specified Mouse Vascular smooth muscle MOVAS lysates 19879844
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Validation: In vivo validation Toggle 893349bafcc528f8346c51dc3420151d67b0126b2c122dd1017121c03fa0f69b
  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 Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4 Filamin-A Co-immunoprecipitation COS-7 19879844
(Link 2bd4d11adb659cddf58197a94e201f0a44c55d8d7cb427c624971b42e122c0a4: click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
TRP / Interactor

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