RT Journal Article
SR Electronic
T1 The channel-kinase TRPM7 regulates antigen gathering and internalization in B cells
JF Science Signaling
JO Sci. Signal.
FD American Association for the Advancement of Science
SP eaah6692
DO 10.1126/scisignal.aah6692
VO 11
IS 533
A1 Krishnamoorthy, Mithunah
A1 Wasim, Laabiah
A1 Buhari, Fathima Hifza Mohamed
A1 Zhao, Tiantian
A1 Mahtani, Trisha
A1 Ho, Josephine
A1 Kang, Sohee
A1 Deason-Towne, Francina
A1 Perraud, Anne-Laure
A1 Schmitz, Carsten
A1 Treanor, Bebhinn
YR 2018
UL http://stke.sciencemag.org/content/11/533/eaah6692.abstract
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.