Glutamate receptors (GluRs) mediate the majority of excitatory neurotransmission in the central nervous system. Regulation of the postsynaptic abundance of GluRs controls the strength of synaptic transmission which plays a critical role in learning and memory. We are interested in identifying genes and mechanisms involved in trafficking GLR-1 GluRs to synapses in the ventral nerve cord (VNC). GLR-1 is an AMPA-type GluR which is expressed in interneurons and localized to synapses in the VNC. Here, we show that APM-2 (also known as DPY-23), the
m2 subunit of the clathrin adaptor AP2, regulates the abundance of GLR-1 in the VNC. AP2 is well known as a regulator of clathrin-mediated endocytosis at the plasma membrane. Surprisingly, we found that
apm-2(
gm17) and
apm-2(
e840) loss-of-function mutants have reduced levels of GLR-1 in the VNC. This effect can be rescued by expression of wild type
apm-2 cDNA in the
glr-1-expressing interneurons. In addition, expression of
apm-2 under a heat-shock inducible promoter at the L4 stage can rescue the GLR-1 defect observed in
apm-2 mutants, suggesting that APM-2 can function in the mature nervous system to regulate GLR-1. In contrast, mutation of another clathrin adaptin UNC-11/AP180, which regulates endocytosis of GLR-1 at synapses, results in accumulation of GLR-1 in the VNC. Interestingly,
apm-2;
unc-11 double mutants exhibit reduced levels of GLR-1 at synapses suggesting that
apm-2 functions prior to GLR-1 endocytosis in the VNC. We hypothesize that APM-2 regulates anterograde trafficking of GLR-1 from the cell body to synapses. Consistent with this idea, GLR-1 accumulates in cell bodies of
apm-2 mutants and genetic double mutant analysis indicates that
apm-2 functions in the same pathway as the kinesin
klp-4, which is involved in anterograde transport of GLR-1. Our data reveal a novel function for APM-2 in regulating the levels of GLR-1 in the VNC and suggest that APM-2, and possibly the AP2 complex, regulate anterograde trafficking of GluRs. Several possible models of how APM-2 regulates GLR-1 trafficking will be discussed.