Abstract
Ca 2+ influx from the extracellular milieu is triggered by store-operated channels (SOCs), whose activity requires association with inositol 1,4,5-trisphosphate (IP 3 ) receptors (IP 3 Rs). Human Trp (transient receptor potential) proteins are thought to be subunits of the SOCs, and IP 3 Rs can interact with Trp proteins, leading to Trp activation. The role of Ca 2+ on Trp function, however, is not clear. Zhang et al. now show that Ca 2+ bound to calmodulin (CaM) can inhibit Trp activity. Increasing concentrations of Ca 2+ -CaM competed off IP3R binding to Trp3, and mapping experiments indicated that Ca 2+ -CaM and IP 3 R compete for mutually exclusive, overlapping binding sites on Trp3. Application of Ca 2+ to "inside-out" membrane patches containing Trp channels strongly inhibited Trp activity, whereas in different membrane patches, the expression of a Ca 2+ -binding mutant of CaM activated Trp3. In the absence of CaM, Trp3 channels exhibited high basal activity, thus these data suggest that CaM is an important regulator of IP 3 R-mediated Trp activation. Z. Zhang, J. Tang, S. Tikunova, J. D. Johnson, Z. Chen, N. Qin, A. Dietrich, E. Stefani, L. Birnbaumer, M. X. Zhu, Activation of Trp3 by inositol 1,4,5-trisphosphate receptors through displacement of inhibitory calmodulin from a common binding domain. Proc. Natl. Acad. Sci. U.S.A. 98 , 3168-3173 (2001). [Abstract] [Full Text]
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