The intrinsic guanosine triphosphatase (GTPase) activity of heterotrimeric G proteins is increased by RGS (regulators of G protein signaling) proteins. Oliveira-dos-Santos et al. identified a role for RGS2 in T cell activation. In response to T cell receptor (TCR) engagement, amounts of rgs2 mRNA and protein increase; however, in rgs2-/- T cells, proliferation and IL-2 production are decreased. rgs2-/- T cells treated with phorbol myristate acetate (PMA) and ionomycin also exhibited defective proliferation, indicating that in rgs2-/- animals the defect lies distal to TCR activation. Defective T cell proliferation was manifested by reduced immunity to viral infection in rgs2-/- mice. Male, but not female, rgs2-deficient mice also exhibited decreased aggression and increased anxiety. Motor skills and cognition appeared unaffected. Gross examination of hippocampi revealed that CA1 neurons from rgs2-/- mice had reduced numbers of apical and basal spines (and possibly fewer synapses), and reduced electrical activity. Thus, further research into the signaling pathway(s) mediated by RGS2 in the brain may lead to the development of neuropsychiatric agents that control anxiety and aggression.
Oliveira-dos-Santos, A.J., Matsumoto, G., Snow, B.E., Bai, D., Houston, F.P., Whishaw, I.Q., Mariathasan, S., Sasaki, T., Wakeham, A., Ohashi, P.S., Roder, J.C., Barnes, C.A., Siderovski, D.P., and Penninger, J.M. (2000) Regulation of T cell activation, anxiety, and male aggression by RGS2. Proc. Natl. Acad. Sci. U.S.A. 97: 12272-12277. [Abstract] [Full Text]