PT  - JOURNAL ARTICLE
AU  - Krishnamoorthy, Mithunah
AU  - Wasim, Laabiah
AU  - Buhari, Fathima Hifza Mohamed
AU  - Zhao, Tiantian
AU  - Mahtani, Trisha
AU  - Ho, Josephine
AU  - Kang, Sohee
AU  - Deason-Towne, Francina
AU  - Perraud, Anne-Laure
AU  - Schmitz, Carsten
AU  - Treanor, Bebhinn
TI  - The channel-kinase TRPM7 regulates antigen gathering and internalization in B cells
AID  - 10.1126/scisignal.aah6692
DP  - 2018 Jun 05
TA  - Science Signaling
PG  - eaah6692
VI  - 11
IP  - 533
4099  - http://stke.sciencemag.org/content/11/533/eaah6692.short
4100  - http://stke.sciencemag.org/content/11/533/eaah6692.full
SO  - Sci. Signal.2018 Jun 05; 11
AB  - 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.