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. Changes in synaptic AMPA receptor levels have been proposed to be a key regulatory event in synaptic plasticity and learning and memory. While the local, synapse-specific regulation of AMPA receptors has been intensely studied, the 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 is required for efficient production of GLR-1 in the AVE interneurons in the nematode Caenorhabditis elegans. In grld-1 mutants, GLR-1 levels were drastically reduced. Consistently, both glutamate-induced currents in AVE and glr-1-dependent nose-touch avoidance behavior were 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.