Direct binding of [alpha]-actinin enhances TRPP3 channel activity

• Published in: Journal of neurochemistry Vol. 103; no. 6; p. 2391
• Main Authors: Li, Qiang, Dai, Xiao-Qing, Shen, Patrick Y, Wu, Yuliang, Long, Wentong, Chen, Carl X, Hussain, Zahir, Wang, Shaohua, Chen, Xing-Zhen
• Format: Journal Article
• Language: English
• Published: New York Blackwell Publishing Ltd 01-12-2007
• Subjects: Binding sites; Biochemistry; Cellular biology; Neurology; Proteins
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2007.04940.x

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 ABSTRACT]