Editors' ChoiceImmunology

Highlight: Distinct functions of the ion channel–kinase TRPM7

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Science Signaling  05 Jun 2018:
Vol. 11, Issue 533, eaau3545
DOI: 10.1126/scisignal.aau3545

Two studies in this week’s issue of Science Signaling identify distinct activities of the ion channel–kinase TRPM7 that control discrete functions in B cells.

The transient receptor potential subfamily M member 7 (TRPM7) is an unusual divalent cation channel that also contains a kinase domain. Critical for the maintenance of cellular Mg2+ balance in various immune cell types, this channel-kinase regulates cell survival, migration, and effector functions. In this issue of Science Signaling, two papers highlight the distinct contributions of TRPM7 ion channel and kinase activities to various B cell functions. To determine the role of TRPM7 in B cell development, Krishnamoorthy et al. analyzed mice lacking TRPM7 specifically in the B cell lineage. They found that loss of TRPM7, but not its kinase activity, blocked B cell precursor development, resulting in a complete absence of mature peripheral B cells. In an in vitro model of B cell development, supplementation with extracellular Mg2+ partially rescued the effects of TRPM7 deficiency, suggesting that the ion channel activity of TRPM7 was required.

In contrast, using total internal reflection fluorescence (TIRF) microscopy to analyze a B cell line and mature B cells, Krishnamoorthy et al. found that the kinase activity of TRPM7 controlled actin dynamics, which are important for the first steps of B cell receptor (BCR)–mediated antigen recognition. When B cells encounter their specific antigen, they aggregate antigen-engaged BCRs into clusters that promote signaling, which leads to antigen internalization required for presentation to T cells. In B cells lacking TRPM7 or TRPM7 kinase activity, more antigen accumulated on the cell surface and activated stronger BCR-dependent signaling, indicating a role for TRPM7 kinase activity in antigen gathering. However, loss of kinase activity did not prevent BCR-mediated antigen internalization, suggesting that TRPM7 ion flux may also be important for internalization. Indeed, an inhibitor of TRPM7 ion channel activity reduced antigen internalization and presentation to T cells. Together, these studies suggest that distinct functions of TRPM7 control specific activities of B lineage cells necessary for development and function.

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