The Role of Magnesium in B-lymphocytes. As opposed to Ca2+, the role of change in intracellular Mg2+-concentrations, [Mg2+]i, in lymphocyte activation remains unclear. Yet Mg2+ is the most abundant intracellular cation, and an essential cofactor for many cellular enzymes, as well as a critical regulator of cell growth and differentiation. A main difficulty in studying the relevance of [Mg2+]i in B-cell activation has been the very poor understanding of molecular mechanisms underlying Mg2+-homeostasis regulation in vertebrates. The Mg2+-permeable ion channel TRPM7, a member of the newly discovered TRPM-subfamily of cation channels, plays an essential role in Mg2+-homeostasis in DT40 B-lymphocytes in such that TRPM7 deficient DT40 B-cells become Mg2+-deficient, experience growth arrest within 24 hr and eventually die. Both, viability and proliferation of TRPM7 deficient DT40 B-cells are rescued by supplementation of Mg2+ to the growth media.For a better understanding of Mg2+-physiology and of Mg2+-dependent signaling events in immune cells, the focus of my research is to investigate the role of TRPM7 and the newly discovered mitochondrial Mg2+-transporter Mrs2 in B-lymphocytes after receptor stimulation, and to analyze their involvement in Mg2+-homeostasis as well as Mg2+-dependent signaling events including PLCg activation.
Perraud AL, Knowles HM, Schmitz C.: Novel aspects of signaling and ion-homeostasis regulation in immunocytes. The TRPM ion channels and their potential role in modulating the immune response. Mol Immunol.; 41(6-7):657-73, 2004.
Ryuichi Takezawa, Carsten Schmitz, Philippe Demeuse, Andrew M. Scharenberg, Reinhold Penner and Andrea Fleig: Receptor-mediated regulation of TRPM7 channel through its endogenous protein kinase domain. Proc Natl Acad Sci U S A. 101(16): 6009-14, 2004.
Carsten Schmitz, Anne-Laure Perraud, Andrea Fleig and Andrew M. Scharenberg: Dual function ion channel/protein kinases: novel components of vertebrate Mg2+ regulatory mechanisms. Pediatric Research, 55: 734-737, 2004.
Anne-Laure Perraud, Carsten Schmitz and Andrew M. Scharenberg: TRPM2 Ca2+ permeable cation channels: from gene to biological function. Cell Calcium 33, 519-531, 2003.
Carsten Schmitz, Anne-Laure Perraud, Kazunori Inabe, Catherine O. Johnson, Megan K. Smith, Reinhold Penner, Tomohiro Kurosaki, Andrea Fleig, and Andrew M. Scharenberg: Regulation of vertebrate cellular Mg2+ -homeostasis by TRPM7. Cell (114), 191-200, 2003.