Functional Characterisation of a TRPM2 orthologue from the sea anemone Nematostella vectensis in human cells

The human non-selective cation channel TRPM2 represents a mediator of apoptosis triggered by oxidative stress. The principal agonist ADP-ribose binds to the cytosolic domain of TRPM2, which is homologous to the human ADP-ribose pyrophosphatase NUDT9. To further elucidate the structure-function relat...

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Bibliographic Details
Published in:Scientific reports 2015-01, Vol.5 (1), p.8032-8032, Article 8032
Main Authors: Kühn, Frank J. P., Kühn, Cornelia, Lückhoff, Andreas
Format: Article
Language:English
Subjects:
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Amino acids
Animals
Apoptosis
Calcium (intracellular)
Calcium - metabolism
Cell Line
Channel gating
Clonal deletion
Enzymes
Humanities and Social Sciences
Humans
Hypotheses
Intracellular
Kinetics
multidisciplinary
Oxidative Stress
Patch-Clamp Techniques
Physiology
Pyrophosphatase
Pyrophosphatases - genetics
Ribose
Science
Sea Anemones - genetics
Structure-function relationships
Transient receptor potential proteins
TRPM Cation Channels - genetics
TRPM Cation Channels - metabolism
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Summary:The human non-selective cation channel TRPM2 represents a mediator of apoptosis triggered by oxidative stress. The principal agonist ADP-ribose binds to the cytosolic domain of TRPM2, which is homologous to the human ADP-ribose pyrophosphatase NUDT9. To further elucidate the structure-function relationship of this channel, we characterised a TRPM2 orthologue from the cnidarian Nematostella vectensis , after its expression in a human cell line. This far distant relative shows only 31% total sequence similarity to h TRPM2, while its C-terminal domain has a greater resemblance to the NUDT9 enzyme. Current through nv TRPM2 was induced by ADPR, with a more pronounced sensitivity and faster kinetics than in h TRPM2. In contrast to h TRPM2, there was no response to H 2 O 2 and hardly any modulatory effect by intracellular Ca 2+ . The deletion of a stretch of 15 residues from the NUDT9 domain of nv TRPM2, which is absent in h TRPM2, did not change the response to ADPR but enabled activation of the channel by H 2 O 2 and increased the effects of intracellular Ca 2+ . These findings shed new light on the evolution of TRPM2 and establish nv TRPM2 as a promising tool to decipher its complex gating mechanisms.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep08032