Phosphatidylinositol 4,5-bisphosphate (PIP2) plays a central role in the activation of several transient receptor potential (TRP) channels. The role of PIP2 on temperature gating of thermoTRP 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 coldsensitive (TRPM8) and heat-sensitive (TRPV1) channels, trying to understand the role of the segment in PIP2 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 PIP2 and confers the phenotype of heat activation. PIP2, 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, PIP2, and voltage. We provide an interpretation for channel-PIP2 interaction using a full-atom molecular model of TRPV1 and PIP2 docking analysis. chimera ͉ temperature activation ͉ C-terminal domain ͉ molecular model P hosphatidylinositol 4,5-bisphosphate (PIP 2 ) acts as a second messenger phospholipid and is the source of another three lipidic-derived messengers (DAG, IP 3 , PIP 3 ). Although the amount of PIP 2 in the membrane is very low, it is able to regulate the activity of ion channels transporters and enzymes (1-3). Several TRP channels reveal some degree of PIP 2 dependence. PIP 2 depletion inhibits TRPM7, TRPM5, TRPM8, TRPV5, and TRPM4 currents (4-9). In the case of TRPM8, some key positively charged residues present in a well conserved sequence contained in the C-terminal region of TRP channels, the TRP domain, were found to be crucial in determining the apparent affinity of PIP 2 activation (7). Residues K995, R998, and R1008 in the TRP box and TRP domain are critically involved in the activation of TRPM8 by PIP 2 . The hydrolysis of PIP 2 also constitutes an important mechanism for the Ca 2ϩ -dependent desensitization of TRPM8 (6, 7). Because of the high sequence similarity among TRP channels in the TRP domain region, it has been proposed that the family of TRP channels possesses a common PIP 2 -binding site located on its proximal C terminus (7, 10, 11). Different from its counterparts, TRPV1 shows a PLC/ NGF-dependent inhibition (12), where binding of NGF to trkA is coupled to PLC activation that leads to PIP 2 hydrolysis. Mutagenesis experiments suggested the presence of a PIP 2 -dependent inhibitory domain (13). In this model, the sensitization observed in TRPV1 is explained on the basis of PIP 2 hydrolysis as it acts as a tonical inhibitor. An alternative model has been proposed for the inhibition based on NGF-dependent phosphorylation of the TRPV1 C-terminal domain and a subsequent increase in membrane expression (14). These observations, together with the finding that...

Modern agriculture relies on mineral fertilization. Unlike other major macronutrients, potassium (K+) is not incorporated into organic matter but remains as soluble ion in the cell sap contributing up to 10% of the dry organic matter. Consequently, K+ constitutes a chief osmoticum to drive cellular expansion and organ movements, such as stomata aperture. Moreover, K+ transport is critical for the control of cytoplasmic and luminal pH in endosomes, regulation of membrane potential, and enzyme activity. Not surprisingly, plants have evolved a large ensemble of K+ transporters with defined functions in nutrient uptake by roots, storage in vacuoles, and ion translocation between tissues and organs. This review describes critical transport proteins governing K+ nutrition, their regulation, and coordinated activity, and summarizes our current understanding of signaling pathways activated by K+ starvation.

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