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Direct binding of α‐actinin enhances TRPP3 channel activity
Author(s) -
Li Qiang,
Dai XiaoQing,
Shen Patrick Y.,
Wu Yuliang,
Long Wentong,
Chen Carl X.,
Hussain Zahir,
Wang Shaohua,
Chen XingZhen
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04940.x
Subject(s) - microbiology and biotechnology , sodium channel , biology , actinin , ion channel , mechanosensation , transient receptor potential channel , mechanosensitive channels , stretch activated ion channel , chemistry , cytoskeleton , biochemistry , receptor , cell , organic chemistry , sodium
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 α‐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 α‐actinin. The TRPP3‐α‐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 α‐actinin‐2. Taken together, α‐actinin not only attaches TRPP3 to the cytoskeleton but also up‐regulates TRPP3 channel function. It remains to be determined whether the TRPP3‐α‐actinin interaction is relevant to acid sensing and other functions in neuronal and non‐neuronal cells.