GRLD-1 regulates cell-wide abundance of glutamate receptor through post-transcriptional regulation

AMPA receptors mediate most of the fast postsynaptic response at glutamatergic synapses. The abundance of AMPA receptors in neurons and at postsynaptic membranes is tightly regulated. It has been suggested that changes in synaptic AMPA receptor levels are an important regulatory event in synaptic plasticity and learning and memory. Although the local, synapse-specific regulation of AMPA receptors has been intensely studied, global, cell-wide control is less well understood. Using a forward genetic approach, we identified glutamate receptor level decreased-1 (GRLD-1), a putative RNA-binding protein that was required for efficient production of GLR-1 in the AVE interneurons in the nematode Caenorhabditis elegans. In grld-1 mutants, GLR-1 levels were markedly reduced. Consistently, glutamate-induced currents in AVE were diminished and glr-1-dependent nose-touch avoidance behavior was defective in grld-1 mutants. We propose that this evolutionarily conserved family of proteins controls the abundance of GLR-1 by regulating glr-1 transcript splicing.