Calmodulin Inhibits Trp3 Function

Sci. STKE, 20 March 2001
Vol. 2001, Issue 74, p. tw3
DOI: 10.1126/stke.2001.74.tw3
Calcium Channels

Calmodulin Inhibits Trp3 Function

Ca2+ influx from the extracellular milieu is triggered by store-operated channels (SOCs), whose activity requires association with inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs). Human Trp (transient receptor potential) proteins are thought to be subunits of the SOCs, and IP3Rs can interact with Trp proteins, leading to Trp activation. The role of Ca2+ on Trp function, however, is not clear. Zhang et al. now show that Ca2+ bound to calmodulin (CaM) can inhibit Trp activity. Increasing concentrations of Ca2+-CaM competed off IP3R binding to Trp3, and mapping experiments indicated that Ca2+-CaM and IP3R compete for mutually exclusive, overlapping binding sites on Trp3. Application of Ca2+ to "inside-out" membrane patches containing Trp channels strongly inhibited Trp activity, whereas in different membrane patches, the expression of a Ca2+-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 IP3R-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]

Citation:

Calmodulin Inhibits Trp3 Function. Sci. STKE 2001, tw3 (2001).
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882