Characterization of a Novel synGAP Isoform, synGAP-β

We cloned a cDNA encoding a novel synGAP, syn-GAP-d (GenBank™ accession number AB016962), from a rat brain cDNA library. The clone consisted of 4801 nucleotides with a coding sequence of 3501 nucleotides, encoded a protein consisting of 1166 amino acids with >99% homology with 1092 amino acid overlaps to syn-GAP, and contained a 13-nucleotide insertion to the previously reported synGAP mRNAs, which suggested that the clone was a splice variant of synGAP. We also found that there are at least seven variants in the 3′ portion of the synGAP mRNA and that they encoded five different protein isoforms. The coding sequence of these C-terminal variants were classified into α1, α2, α1, α2, α3, α4, and γ, and synGAP-d was classified as the β1 form. The previously reported synGAPs (synGAP-a, -b, and -c and p135synGAP) can be classified as the α1 isoform. All isoforms were expressed specifically in the brain. Unexpectedly, the β isoform, which lacks a C-terminal PSD95-binding motif ((S/T)XV), was more restricted to the postsynaptic density fraction than the motif-containing α1 isoform. The β isoform did not interact with PSD-95 but specifically interacted with a nonphosphorylated α subunit of Ca²⁺/calmodulin-dependent protein kinase II through its unique C-terminal tail.