"These results suggest that LRIT3 facilitates exit of FGFR1 from the ER."

"Perhaps highly over-expressed FGFR1s can interact and phosphorylate each other at the cell surface without a ligand [22]. Alternatively, stabilization and over-expression of FGFR1 simply allow cells to respond to even small amounts of growth factors in the culture medium (serum) rather than these cells become truly FGF-independent. Although the exact mechanism of action is not clear, our results strongly suggest that LRIT3 facilitates ER export of FGFR1, that FGFR1 exits the ER not in a constitutive fashion, but in a regulated fashion, and that LRIT3 modulates the FGFR-signaling pathway."

"Whole-exome sequencing in one simplex cCSNB case lacking mutations in the known genes led to the identification of a missense mutation (c.983G>A [p.Cys328Tyr]) and a nonsense mutation (c.1318C>T [p.Arg440(∗)]) in LRIT3, encoding leucine-rich-repeat (LRR), immunoglobulin-like, and transmembrane-domain 3 (LRIT3). Subsequent Sanger sequencing of 89 individuals with CSNB identified another cCSNB case harboring a nonsense mutation (c.1151C>G [p.Ser384(∗)]) and a deletion predicted to lead to a premature stop codon (c.1538_1539del [p.Ser513Cysfs(∗)59]) in the same gene."

"Human LRIT3 antibody staining revealed in the outer plexiform layer of the human retina a punctate-labeling pattern resembling the dendritic tips of bipolar cells; similar patterns have been observed for other proteins implicated in cCSNB."

"Finally, synaptic contacts made by ON-BC but not OFF-BC neurons with the cone pedicles were disorganized without ultrastructural alterations in cone terminals, horizontal cell processes, or synaptic ribbons."

"CONCLUSIONS: These results suggest that LRIT3 is likely involved in coordination of the transsynaptic communication between cones and ON-BCs during synapse formation and function."

"In contrast, we demonstrate that LRIT3 is expressed presynaptically, in rod photoreceptors (rods), and when we restore LRIT3 expression in Lrit3-/- rods, we restore expression of the postsynaptic glutamate signalplex and rod-driven vision."

"Our results demonstrate that, in the retina, the LRR-containing protein LRIT3 acts as a transsynaptic organizer of the postsynaptic complex required for normal synaptic function."

"In both male and female mice, we demonstrate that LRIT3 interacts with and is required for expression of nyctalopin, and thus TRPM1 at all DBC dendritic tips, but DBC signalplex components are not required for LRIT3 expression."

"Using whole-cell and multielectrode array (MEA) electrophysiology and glutamate imaging, we demonstrate that the loss of LRIT3 impacts both ON and OFF signaling pathway function. Without LRIT3, excitatory input to type 1 BCs is reduced, as are the visually evoked responses of many OFF retinal ganglion cells (RGCs). We conclude that the absence of LRIT3 expression disrupts excitatory input to OFF BCs and, thus disrupts the normal function of OFF RGCs."

"These observations suggest that LRIT3 is confined to pre-synaptic compartment and is expressed solely by photoreceptors."

"This indicates that LRIT3 is prominently present in cone synapses too and confirms its pre-synaptic origin."

"The IG domain is required for the localization of TRPM1 to the signalplex and thus its function."

"We show the LRR domain may be required for trafficking LRIT3 to the synapse in cones, but not rods, and it is needed for reassembly and function of the rod BC signalplex."