Shaping of Signal Transmission at the Photoreceptor Synapse by EAAT2 Glutamate Transporters

Abstract

Photoreceptor ribbon synapses tonically release glutamate. In order to ensure efficient signal transmission and prevent glutamate toxicity, a highly efficient glutamate removal system provided by members of the SLC1 gene family is required. By using a combination of biophysical and in vivo studies we elucidate the role of EAAT2 proteins in synaptic glutamate homeostasis at the zebrafish photoreceptor synapse. The main glutamate sink is provided by the glial EAAT2a, reflected by reduced electroretinographic responses in EAAT2a depleted larvae. EAAT2b is located on the tips of cone pedicles and contributes little to glutamate re-uptake. However, this transporter displays both a large chloride conductance and leak current, being important in stabilizing the cone resting potential. This work not only demonstrates how proteins originating from the same gene family can complement each other’s expression profiles and biophysical properties, but also how presynaptic and glial transporters are coordinated to ensure efficient synaptic transmission at glutamatergic synapses of the central nervous system.

Significance Statement Glutamate transporters are key regulators of glutamate homeostasis. Here we analyze two players of glutamate homeostasis at the zebrafish photoreceptor synapse. This report demonstrates how paralogous glutamate transporters emerging from a whole genome duplication event acquired a complementary expression pattern and adopted different biophysical characteristics that allow modulation of the synapse and signal transmission in a specialized manner.