Regulation of T cell activation, anxiety, and male aggression by RGS2

Regulation of T cell activation, anxiety, and male aggression by RGS2

^*Amgen Institute and ^¶Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, University of Toronto, 620 University Avenue, Toronto, ON M5G 2C1 Canada; ^†Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON M5S1A8 Canada; ^‡Arizona Research Laboratories, Division of Neural Systems, Memory, and Aging, University of Arizona, Tucson, AZ 85724; ^§Department of Psychology, University of Lethbridge, AB T1K3 M4 Canada; and ^‖Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599

Communicated by Alfred G. Gilman, University of Texas Southwestern Medical Center, Dallas, TX (received for review June 20, 2000)

Abstract

Regulators of G protein signaling (RGS) proteins accelerate the GTPase activity of Gα protein subunits in vitro, negatively regulating G protein-coupled receptor signaling. The physiological role of mammalian RGS proteins is largely unknown. The RGS family member rgs2 was cloned as an immediate early response gene up-regulated in T lymphocytes after activation. To investigate the role of RGS2 in vivo, we generated rgs2-deficient mice. We show that targeted mutation of rgs2 in mice leads to reduced T cell proliferation and IL-2 production, which translates in an impaired antiviral immunity in vivo. Interestingly, rgs2 ^−/− mice also display increased anxiety responses and decreased male aggression in the absence of cognitive or motor deficits. RGS2 also controls synaptic development and basal electrical activity in hippocampal CA1 neurons. Thus, RGS2 plays an important role in T cell activation, synapse development in the hippocampus, and emotive behaviors.

Footnotes

↵ ** To whom reprint requests should be addressed. E-mail: jpenning{at}amgen.com.
Article published online before print: Proc. Natl. Acad. Sci. USA, 10.1073/pnas.220414397.
Article and publication date are at www.pnas.org/cgi/doi/10.1073/pnas.220414397
Abbreviations:

GPCR,

G protein-coupled receptors;

GAP,

GTP-activating;

RGS,

regulators of G protein signaling;

CNS,

central nervous system;

ES,

embryonic stem;

LCMV,

lymphocytic choriomeningitis virus;

EPSP,

excitatory postsynaptic potentials