Abstract
SUMMARYCone photoreceptors scale dynamically the sensitivity of responses to maintain responsiveness across wide range of changes in luminance. Synaptic changes contribute to this adaptation, but how this process is coordinated at the molecular level is poorly understood. Here, we report that a cell adhesion-like molecule, LRIT1, is enriched selectively at cone photoreceptor synapses where it engages in a trans-synaptic interaction with mGluR6, the principal receptor in postsynaptic ON-bipolar cells. The levels of LRIT1 are regulated by the neurotransmitter release apparatus that controls photoreceptor output. Knockout of LRIT1 in mice increases the sensitivity of cone synaptic signaling while impairing its ability to adapt to background light without overtly influencing the morphology or molecular composition of photoreceptor synapses. Accordingly, mice lacking LRIT1 show visual deficits under conditions requiring temporally challenging discrimination of visual signals in steady background light. These observations reveal molecular mechanisms involved in scaling synaptic communication in the retina.
Highlights
In the vertebrate retina, the rod and cone photoreceptors respond to incident light by modulating their membrane potential
We found 4 peptides with high identification confidence that map to the sequence of the transmembrane protein, LRIT1 (Figure 1B)
When probing blots with our anti-LRIT1 antibodies, we found a single band corresponding to the predicted size of LRIT1 protein in the eluates of wild-type but not nob3 retinas, confirming the specificity of LRIT1-mGluR6 interaction in native retinas (Figure 1D)
Summary
The rod and cone photoreceptors respond to incident light by modulating their membrane potential. This signal is transmitted to their bipolar cells and eventually to higher visual centers that enable our complex visual experience. Cones are less sensitive, but faster, cover a wider range of light intensities, and are more resistant to saturation than rods (Burkhardt, 1994; Matthews et al, 1990; Nikonov et al, 2006). Cones normally operate under daylight conditions where light intensities vary over a wide range, requiring them to adjust dynamically the sensitivity of their responses (Korenbrot, 2012; Soo et al, 2008; Stockman et al, 2006)
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