Exon 4-skipping GLT-1: a new form of an abundantly expressed glutamate transporter

GLT-1 (EAAT2) is an abundant glial glutamate transporter in the mammalian brain. It plays important roles, especially in the termination of neurotransmitter signals at excitatory synapses in grey matter. In normal brain, alternative splicing of GLT-1 has been described, where exons in the GLT-1 gene are skipped or intronic sequences spliced in to generate new sequences. This study describes the isolation of a cDNA clone encoding a new splice variant of GLT-1 where exon 4 is skipped. This novel variant was isolated by RT-PCR cloning from adult rat brain and encodes a protein of 500 amino acids (MW ~54.5 kDa). RT-PCR analysis showed that mRNA was readily detectable in various brain regions of rat, primary astrocyte cultures and in tissues such as testis, but little mRNA was detectable in retina and liver. An antibody that selectively recognizes exon-4 skipping GLT-1 revealed strong signals in Western blots and labelled grey matter astrocytes. We conclude that exon-4 skipping GLT 1 is abundantly expressed in the brain and may represent either a functional glutamate transporter or a modulator of glutamate transporter function.