Effect of thyroid deficiency on Go α-subunit isoforms in developing rat cerebral cortex

Postnatal development of Gα_o isoforms in rat cerebral cortex was studied by SDS-PAGE and immunoblotting. When rat cerebral cortical membranes were resolved on separating gels containing 9% acrylamide and 8 M urea, three electrophoretically distinct Gα_o-immunoreactive proteins were evident. Comparison of their electrophoretic mobilities and partial tryptic digest pattern with recombinant Gα_o1 or Gα_o1-specific antibody revealed that the slowest and intermediate-migrating bands represent unmodified and fatty acylated forms of Gα_o1 protein, respectively. The fastestmigrating band corresponds to Gα_o2. While the fatty acylated form of Gα_o1 is the predominant species, its appearance paralleled that observed for Gα_o2 in developing rat cortex. Perinatal hypothyroidism induced by methimazole treatment did not significantly alter the appearance of cerebral cortical Gα_o1 and Gα_o2 between days 1 and 22 postpartum. Our findings support the earlier idea that heterogeneity of Gα_o proteins in mammalian brain is likely the result of different co- or post-translational processings of each splice variant of Gα_o. While the appearance of Gα_o isoforms is developmentally regulated, they likely do not play an obligatory role in neonatal brain development. Alternatively, the expression of Gα_o isoforms in developing rat cortex may be controlled by an intrinsic signal(s) that is independent of the thyroid status.