Editors' ChoiceChannels

Regulators for LTRPC Channels

Science's STKE  05 Jun 2001:
Vol. 2001, Issue 85, pp. tw8
DOI: 10.1126/stke.2001.85.tw8

TRP channels represent a large family of structurally related ion channels. The LTRP members have long COOH- and NH2-termini, with the COOH-terminus having consensus enzyme domains (see Cahalan). The LTRPC7 channel (also known as TRP-PLIK) was proposed by Runnels et al. to have kinase activity that influenced channel activity, but according to Nadler et al. LTRPC7 is not a kinase. Rather, they conclude that the consensus kinase domain allows the channel to be regulated by binding Mg•ATP without requiring the hydrolysis of the ATP. Furthermore, Nadler et al. suggest that, under physiological conditions, LTRPC7 is selective for divalent cations and is not a nonselective cation channel as previously reported. Perraud et al. show that another member of this family, the LTRPC2 channel, may have a different enzymatic activity, as an adenosine diphosphate (ADP) pyrophosphatase. Indeed, the Nudix homology domain of the LTRPC2 channel, when purified as a recombinant protein from Escherichia coli, is able to specifically hydrolyze ADP in vitro. However, Perraud et al. do not provide evidence for the native or even transfected LTRPC2 channel to have this enzymatic activity. The LTRPC2 channel can be activated by experimental conditions that increase ADP concentrations, suggesting that the interaction with ADP may be relevant. Thus, LTRPC2 and LTRPC7 appear to be ion channels gated by intracellular ligands. It remains to be definitively determined whether they also have enzymatic activity in vivo.

M. D. Calahan, Channels as enzymes. Nature 411, 542-543 (2001). [Online Journal]

L. W. Runnels, L. Yue, D. E. Clapham, TRP-PLIK, a bifunctional protein with kinase and ion channel activities.Science 291, 1043-1047 (2001). [Abstract] [Full Text]

M. J. S. Nadler, M. C. Hermosura, K. Inabe, A.-L. Perraud, Q. Zhu, A. J. Stokes, T. Kurosaki, J.-P. Kinet, R. Penner, A. M. Scharenberg, A. Fleig, LTRPC7 is a Mg•ATP-regulated divalent cation channel required for cell viability. Nature 411, 590-595 (2001). [Online Journal]

A.-L. Perraud, A. Fleig, C. A. Dunn, L. A. Bagley, P. Launay, C. Schmitz, A. J. Stokes, Q. Zhu, M. J. Bessman, R. Penner, J.-P. Kinet, A. M. Scharenberg, ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature 411, 595-599 (2001). [Online Journal]