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Cell Rep. 2019 Jun 11;27(11):3107-3116.e3. doi: 10.1016/j.celrep.2019.05.056.

Presynaptic Expression of LRIT3 Transsynaptically Organizes the Postsynaptic Glutamate Signaling Complex Containing TRPM1.

Author information

1
Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY 40292, USA.
2
Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY 40292, USA.
3
Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
4
Department of Ophthalmology and Visual Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA; Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford OX3 9DU, UK.
5
Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY 40292, USA; Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY 40292, USA.
6
Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY 40292, USA; Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY 40292, USA; Department of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY 40292, USA. Electronic address: ron.gregg@louisville.edu.

Abstract

Throughout the CNS, interactions between pre- and postsynaptic adhesion molecules establish normal synaptic structure and function. Leucine-rich repeat (LRR) domain-containing proteins are a large family that has a diversity of ligands, and their absence can cause disease. At the first retinal synapse, the absence of LRIT3 expression leads to the disassembly of the postsynaptic glutamate signaling complex (signalplex) expressed on depolarizing bipolar cell (DBC) dendrites. The prevalent view is that assembly of the signalplex results from direct postsynaptic protein:protein interactions. 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.

KEYWORDS:

CSNB; LRR proteins; Lrit3; TRPM1; bipolar cells; congenital stationary night blindness; mGluR6; retina; retinal ganglion cells; rod photoreceptors; transsynaptic interactions

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