Differentiation of human T cells alters their repertoire of G protein alpha-subunits.

ABSTRACT: Because T cell differentiation leads to an expanded repertoire of chemokine receptors, a subgroup of G protein-coupled receptors, we hypothesized that the repertoire of G proteins might be altered in parallel. We analyzed the abundance of mRNA and/or protein of six G protein ?-subunits in human CD4(+) and CD8(+) T cell subsets from blood. Although most G protein ?-subunits were similarly expressed in all subsets, the abundance of G?(o), a protein not previously described in hematopoietic cells, was much higher in memory versus naive cells. Consistent with these data, activation of naive CD4(+) T cells in vitro significantly increased the abundance of G?(o) in cells stimulated under nonpolarizing or T(H)17 (but not T(H)1 or T(H)2)-polarizing conditions. In functional studies, the use of a chimeric G protein ?-subunit, G?(qo5), demonstrated that chemokine receptors could couple to G?(o)-containing G proteins. We also found that G?(i1), another ?-subunit not described previously in leukocytes, was expressed in naive T cells but virtually absent from memory subsets. Corresponding to their patterns of expression, siRNA-mediated knockdown of G?(o) in memory (but not naive) and G?(i1) in naive (but not memory) CD4(+) T cells inhibited chemokine-dependent migration. Moreover, although even in G?(o)- and G?(i1)-expressing cells mRNAs of these ?-subunits were much less abundant than G?(i2) or G?(i3), knockdown of any of these subunits impaired chemokine receptor-mediated migration similarly. Together, our data reveal a change in the repertoire of G?(i/o) subunits during T cell differentiation and suggest functional equivalence among G?(i/o) subunits irrespective of their relative abundance.

SUBMITTER: Foley JF 

PROVIDER: S-EPMC2975178 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature