Direct binding of alpha-actinin enhances TRPP3 channel activity

J Neurochem. 2007 Dec;103(6):2391-400. doi: 10.1111/j.1471-4159.2007.04940.x. Epub 2007 Oct 17.

Abstract

Transient receptor potential (TRP) polycystin 2 and 3 (TRPP2 and 3) are homologous members of the TRP superfamily of cation channels but have different physiological functions. TRPP2 is part of a flow sensor, and is defective in autosomal dominant polycystic kidney disease and implicated in left-right asymmetry development. TRPP3 is reported to implicate in sour tasting in bipolar cells of taste buds of the tongue and in the regulation of pH-sensitive action potential in neurons surrounding the central canal of spinal cord. TRPP3 is present in both excitable and non-excitable cells in various tissues, such as retina, brain, heart, testis, and kidney, but its common and cell type-specific functional characteristics remain largely unknown. In this study, we investigated physical and functional interactions between TRPP3 and alpha-actinin, an actin-bundling protein known to regulate several types of ion channels. We employed planer lipid bilayer electrophysiology system to study the function of TRPP3 channel that was affinity-purified from Madin-Darby canine kidney cells. Upon reconstitution in bilayer, TRPP3 exhibited cation channel activities that were substantially augmented by alpha-actinin. The TRPP3-alpha-actinin association was documented by co-immunoprecipitation using native cells and tissues, yeast two-hybrid, and in vitro binding assays. Further, TRPP3 was abundantly present in mouse brain where it associates with alpha-actinin-2. Taken together, alpha-actinin not only attaches TRPP3 to the cytoskeleton but also up-regulates TRPP3 channel function. It remains to be determined whether the TRPP3-alpha-actinin interaction is relevant to acid sensing and other functions in neuronal and non-neuronal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Actinin / metabolism*
  • Animals
  • Calcium Channels / metabolism*
  • Cell Line
  • Cell Membrane / metabolism*
  • Cytoskeleton / metabolism*
  • Dogs
  • Humans
  • Membrane Potentials / physiology
  • Neurons, Afferent / metabolism
  • Protein Binding / physiology
  • Rabbits
  • Receptors, Cell Surface / metabolism*
  • TRPP Cation Channels / metabolism*
  • Up-Regulation / physiology

Substances

  • Calcium Channels
  • PKD2L1 protein, human
  • Receptors, Cell Surface
  • TRPP Cation Channels
  • Actinin