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Polycystin-1 and -2 dosage regulates pressure sensing

Reza Sharif-Naeini1, Joost H A Folgering, Delphine Bichet

  • 1Institut de Pharmacologie Moléculaire et Cellulaire, UMR CNRS 6097, Université de Nice Sophia Antipolis, 06560 Valbonne, France.

Cell
|November 3, 2009
PubMed

Insights

Polycystins TRPP1 and TRPP2 regulate cellular pressure sensing by modulating stretch-activated ion channels (SACs). The TRPP1/TRPP2 ratio and interaction with filamin A are critical for this mechanosensitivity.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Physiology

Background:

  • Autosomal-dominant polycystic kidney disease (ADPKD) is a leading genetic cause of kidney failure, linked to PKD1/PKD2 gene mutations.
  • Polycystins (TRPP1/TRPP2) form ion channels in primary cilia, but their role in cellular mechanosensitivity is unclear.

Purpose of the Study:

  • To elucidate the role of polycystins (TRPP1 and TRPP2) in cellular mechanosensitivity and pressure sensing.
  • To investigate the interaction of polycystins with other cellular components involved in mechanotransduction.

Main Methods:

  • Investigated TRPP2 inhibition of stretch-activated ion channels (SACs).
  • Assessed the effect of TRPP1/TRPP2 ratio on pressure sensing in smooth muscle cells.
  • Examined the interaction between TRPP2 and filamin A.

Main Results:

  • TRPP2 inhibits SACs; TRPP1 coexpression reverses this effect, regulating pressure sensing.
  • TRPP1 deletion in smooth muscle reduces SAC activity and myogenic tone.
  • TRPP2 depletion in TRPP1-deficient arteries restores SAC activity and myogenic response.
  • TRPP2 interacts with filamin A, which is crucial for SAC regulation.

Conclusions:

  • Polycystins play a key role in regulating pressure sensing through modulation of SACs.
  • The TRPP1/TRPP2 ratio and filamin A interaction are critical for arterial mechanosensitivity.

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