LRIT1 Modulates Adaptive Changes in Synaptic Communication of Cone Photoreceptors

• Published in: Cell reports (Cambridge) Vol. 22; no. 13; pp. 3562 - 3573
• Main Authors: Sarria, Ignacio, Cao, Yan, Wang, Yuchen, Ingram, Norianne T., Orlandi, Cesare, Kamasawa, Naomi, Kolesnikov, Alexander V., Pahlberg, Johan, Kefalov, Vladimir J., Sampath, Alapakkam P., Martemyanov, Kirill A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.03.2018; Elsevier
• Subjects: Animals; Cell Line; cone photoreceptors; G protein coupled receptors; HEK293 Cells; Humans; leucine-rich repeat proteins; Membrane Glycoproteins - metabolism; Mice; Mouse Embryonic Stem Cells - metabolism; ON-bipolar neurons; Receptors, Metabotropic Glutamate - metabolism; Retinal Cone Photoreceptor Cells - metabolism; Synapses - metabolism; synaptic transmission; synaptic transmission; cone photoreceptors; ON-bipolar neurons; G protein coupled receptors; leucine-rich repeat proteins
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.03.008

Cone 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. [Display omitted] •LRIT1 is identified as a binding partner of mGluR6 complex in the retina•LRIT1 accumulates at photoreceptor synapses in an activity-dependent manner•Deletion of LRIT1 in mice increases the sensitivity of cone synaptic transmission•Loss of LRIT1 impairs light adaptation of cone synapses and daylight vision Sarria et al. show LRIT1 accumulates at photoreceptors synapses. It forms a complex with a key receptor involved in processing neurotransmitter output of photoreceptors. They show that this protein plays an essential role in synaptic communication of cone photoreceptors and impacts daylight vision.