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Pflügers Archiv

, Volume 451, Issue 1, pp 220–227 | Cite as

TRPM2 and TRPM7: channel/enzyme fusions to generate novel intracellular sensors

  • Andrew. M. ScharenbergEmail author
Invited Review

Abstract

Within the transient receptor potential (Trp) superfamily of ion channels, three members of the Trp (melastatin) (TRPM) subfamily stand out as their amino acid sequences indicate that they possess both ion channel and enzymatic functions. Recently, progress has been made in understanding the relationships between these disparate functionalities for two of these proteins, TRPM2 and TRPM7. TRPM2 appears to have adapted an ADP-ribose hydrolase (ADPRibase) enzyme’s structure as a means of binding ADP-ribose and conveying information about the accumulation of ADP-ribose to the cell via the activation of Na+/Ca2+ entry through the channel domain. While the ADPRibase activity of TRPM2’s enzymatic domain is not required for channel gating, whether a converse relationship exists, wherein channel gating or ion flow modulates the enzymatic domain’s ADPRibase activity, is not known. In contrast, TRPM7 appears to have evolved to place a Mg2+-regulated protein kinase domain in close proximity to a Mg2+-permeant ion channel, such that the kinase domain’s phosphotransferase activity is able respond to local changes in free Mg2+ occurring as the result of the flux of Mg2+ through the channel. As with TRPM2, the activity of TRPM7’s enzymatic domain is not required for gating of its channel domain, although evidence exists that it may have an alternative means of influencing channel gating. These insights into the functional relationships between the channel and enzymatic domains of TRPM2 and TRPM7 suggest informative models for their roles in vertebrate cell physiology.

Keywords

Kinase Domain Channel Gating Mutant Channel TRPM2 Channel Binding Cleft 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

This work was supported by NIH grants GM64091 and GM64316 to A.M.S.

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Children’s Hospital and Regional Medical Center, Department of PediatricsUniversity of WashingtonSeattle

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