VASCULAR POLYCYSTINS · Mechanosensation of the polycystin ion-channels and their role in vascular pathology
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2007-01-01 → 2008-12-31
- EU contribution
- €150,238
- Participants
- 1
- Scheme
- EIF
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Results in brief
Final Activity Report Summary - VASCULAR POLYCYSTINS (Mechanosensation of the polycystin ion-channels and their role in vascular pathology)
Mechanotransduction underlies major physiological functions such as the sense of touch, hearing or arterial pressure sensing. It was suggested that the polycystin complex TRPP1/TRPP2, mutated in autosomal dominant polycystic kidney disease, acted as a flow sensor in the primary cilium of renal and endothelial cells. However, the way in which polycystins contributed to cellular mechanosensitivity remained obscure. Our study showed that, surprisingly, TRPP2, through the actin cross-linking protein filamin A, inhibited stretch-activated ion channels and impaired the arterial myogenic response to intraluminal pressure. This specific effect was reversed by co-expression with TRPP1, indicating that the TRPP1/TRPP2 ratio regulated pressure sensing.
Data: CORDIS, © European Union
Project objective
This project concerns the vascular physiopathology of the receptor-ion channel complex Polycystin1/Polycystin2 (PC1/PC2). Mutations in the PC genes PKD1 and PKD2 provoke autosomal dominant polycystic kidney disease (ADPKD). This is one of the most frequent inherited kidney diseases with a prevalence of about 1/1000. Arterial hypertension, cerebral aneurysms and prolapse of the mitral valve are also associated with ADPKD.The molecular and cellular mechanisms linking PC with the cardio-vascular phenotype are still unknown. Dr. Eric Honore (CNRS, Valbonne) has been working on the molecular physiology of ion channels since several years. His laboratory is currently developing complementary strategies of molecular cloning, proteomic analysis, functional reconstitution, electrophysiology, calcium imaging and transgenics for the study of mechano-sensitive ion channels. We will examine the role of the PC1/PC2 molecular complex in the regulation of vascular calcium homeostasis.Specifically, we will study ion channel activity of PC at the level of both the plasma membrane and the endoplasmic reticulum of vascular smooth muscle and endothelial cells. I will use my expertise in protein purification and functional reconstitution into artificial bilayers to understand the molecular basis of PC mechano-sensitivity. This study will be useful to address the role of PC in vascular physiology. Moreover, these results will provide information concerning the genesis of cerebral aneurysms and arterial hypertension associated with ADPKD.
Original text from CORDIS.
Participants
- CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE · PARISCoordinatorFrance
Links
Data: CORDIS, © European Union