Research ArticleION TRANSPORT

The channel-kinase TRPM7 regulates antigen gathering and internalization in B cells

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Science Signaling  05 Jun 2018:
Vol. 11, Issue 533, eaah6692
DOI: 10.1126/scisignal.aah6692

Ion channel activity controls antigen uptake

The TRPM7 magnesium channel is one of only two ion channels that also contain a kinase domain. This dual ion channel–kinase can phosphorylate nonmuscle myosin IIA heavy chain and control cytoskeletal rearrangements. Using TIRF microscopy, Krishnamoorthy et al. found that expression of TRPM7 in B cells controlled actin dynamics and prevented antigen internalization. In activated B cells lacking TRPM7 or TRPM7 kinase activity, more antigen accumulated on the cell surface and activated stronger B cell receptor–dependent signaling. An inhibitor of TRPM7 ion channel activity reduced antigen presentation to T cells. These data identify a previously uncharacterized role for TRPM7 in B cell antigen uptake and presentation.


Members of the transient receptor potential (TRP) family of ion channels are cellular sensors involved in numerous physiological and pathological processes. We identified the TRP subfamily M member 7 (TRPM7) channel-kinase as a previously uncharacterized regulator of B cell activation. We showed that TRPM7 played a critical role in the early events of B cell activation through both its ion channel and kinase functions. DT40 B cells deficient in TRPM7 or expressing a kinase-deficient mutant of TRPM7 showed defective gathering of antigen and prolonged B cell receptor (BCR) signaling. We showed that lipid metabolism was altered in TRPM7-deficient cells and in cells expressing a kinase-deficient mutant of TRPM7 and suggest that PLC-γ2 may be a target of the kinase activity of TRPM7. Primary B cells that expressed less TRPM7 or were treated with a pharmacological inhibitor of TRPM7 also displayed defective antigen gathering and increased BCR signaling. Finally, we demonstrated that blocking TRPM7 function compromised antigen internalization and presentation to T cells. These data suggest that TRPM7 controls an essential process required for B cell affinity maturation and the production of high-affinity antibodies.

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