Dissection of the components for PIP(2) activation and thermosensation in TRP channels

作者：Brauchi Sebastian^*; Orta Gerardo; Mascayano Carolina; Salazar Marcelo; Raddatz Natalia; Urbina Hector; Rosenmann Eduardo; Gonzalez Nilo Fernando; Latorre Ramon

来源：Proceedings of the National Academy of Sciences, 2007, 104(24): 10246-10251.

DOI：10.1073/pnas.0703420104

• chimera
• temperature activation
• C-terminal domain
• molecular model

Phosphatidylinositol 4,5-bisphosphate (PIPA plays a central role in the activation of several transient receptor potential (TRIP) channels. The role of PIP(2) on temperature gating of thermo TRP channels has not been explored in detail, and the process of temperature activation is largely unexplained. In this work, we have exchanged different segments of the C-terminal region between cold-sensitive (TRPM8) and heat-sensitive (TRPV1) channels, trying to understand the role of the segment in PIP(2) and temperature activation. A chimera in which the proximal part of the C-terminal of TRPV1 replaces an equivalent section of TRPM8 C-terminal is activated by PIP(2) and confers the phenotype of heat activation. PIP(2), but not temperature sensitivity, disappears when positively charged residues contained in the exchanged region are neutralized. Shortening the exchanged segment to a length of 11 aa produces voltage-dependent and temperature-insensitive channels. Our findings suggest the existence of different activation domains for temperature, PIP(2), and voltage. We provide an interpretation for channel-PIP(2) interaction using a full-atom molecular model of TRPV1 and PIP(2) docking analysis.

• 出版日期2007-6-12
• 单位上海生物信息技术研究中心