Trans-activation Response (TAR) RNA-binding Protein 2 Is a Novel Modulator of Transient Receptor Potential Canonical 4 (TRPC4) Protein |
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Authors: | Jasmin Zimmermann Lorenz Latta Andreas Beck Petra Leidinger Claudia Fecher-Trost Gabriel Schlenstedt Eckart Meese Ulrich Wissenbach Veit Flockerzi |
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Institution: | From the ‡Institut für Experimentelle und Klinische Pharmakologie und Toxikologie.;§Institut für Humangenetik, and ;¶Institut für Medizinische Biochemie und Molekularbiologie, Universität des Saarlandes, 66421 Homburg, Germany |
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Abstract: | TRPC4 proteins function as Ca2+ conducting, non-selective cation channels in endothelial, smooth muscle, and neuronal cells. To further characterize the roles of TRPC4 in vivo, detailed information about the molecular composition of native channel complexes and their association with cellular signaling networks is needed. Therefore, a mouse brain cDNA library was searched for novel TRPC4-interacting proteins using a modified yeast two-hybrid assay. This screen identified Trans-activation Response RNA-binding protein 2 (Tarpb2), a protein that recruits the Dicer complex to Ago2 for microRNA processing and gene silencing. Tarbp2 was found to bind to the C terminus of TRPC4 and TRPC5 and to modulate agonist-dependent TRPC4-induced Ca2+ entry. A stretch of basic residues within the Tarbp2 protein is required for these actions. Tarbp2 binding to and modulation of TRPC4 occurs in the presence of endogenously expressed Dicer but is no longer detectable when the Dicer cDNA is overexpressed. Dicer activity in crude cell lysates is increased in the presence of Ca2+, most probably by Ca2+-dependent proteolytic activation of Dicer. Apparently, Tarbp2 binding to TRPC4 promotes changes of cytosolic Ca2+ and, thereby, leads to a dynamic regulation of Dicer activity, essentially at low endogenous Dicer concentrations. |
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Keywords: | Calcium Signaling Cell Signaling Dicer Protein-Protein Interactions TRP Channels |
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