Differential distribution of synGAPα1 and synGAPβ isoforms in rat neurons

Abstract: The synaptic Ras-GTPase activating protein synGAP is a brain-specific protein of approximately 130 kDa and is a negative regulator of Ras. We previously reported 5 C-terminal isoforms of synGAP (α1, α2, β1/2, β3/4 and γ) [Li et al., 2001, J. Biol. Chem. 276: 21417–21424]. In this study, we investigated the expression profiles of the two major isoforms, synGAPα1 and synGAPβ, in the adult rat brain and cultured neurons of the rat hippocampus. Examination of pepsin-pretreated brain sections demonstrated that both isoforms were expressed mainly in the forebrain structures, which suggests their association with postsynaptic density. The distribution of the synGAPα1 and β (β1–4) isoforms in the adult rat brain was clearly different in cerebellum, hippocampus, cerebral cortex, septum and olfactory bulb. In particular, synGAPα1 was specifically localized to the cerebellar glomeruli, dense synaptic sites. From the analysis using cultured neurons, unique expression of synGAPβ was found in a neuron with a sea urchin-like morphology, possibly a star pyramidal neuron, in which the synGAPβ expression was relatively high, in particular, at the distal part of its processes. SynGAPα1 was mostly or specifically localized to excitatory postsynaptic sites, whereas synGAPβ was present at both excitatory and inhibitory postsynaptic sites. Finally, there are more non-synaptic clusters in dendrites in the case of synGAPβ than synGAPα1. Thus, the two synGAP isoforms, α1 and β, distribute differently in neuronal cells and the brain. [Copyright &y& Elsevier]