title: TRPM1 forms complexes with nyctalopin in vivo and accumulates in postsynaptic compartment of ON-bipolar neurons in mGluR6-dependent manner.
abstract: Synaptic transmission between light-sensory photoreceptor cells and downstream ON-bipolar neurons plays an important role for vertebrate vision. This process is mediated by the G-protein-coupled receptor pathway involving glutamate receptor mGluR6 and effector channel TRPM1. The signal transmission occurs on a rapid timescale; however, the molecular organization that ensures timely signaling in this cascade is unknown. Genetic studies in human patients and animal models reveal that ON-bipolar cell signaling depends on the synaptic protein nyctalopin. We have conducted a proteomic search for proteins associated with nyctalopin in the mouse retina and identified TRPM1 as the binding partner. We further demonstrate that nyctalopin additionally interacts with mGluR6 receptor. Disruption of mGluR6 prevented targeting of TRPM1 to the postsynaptic compartment of ON-bipolar neurons. These results reveal a unique macromolecular organization of the mGluR6 cascade, where principal signaling components are scaffolded by nyctalopin, creating an organization essential for the correct localization of the signaling ensemble and ultimately intact transmission of the signal at the first visual synapse.
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, Jupiter, Florida 33458, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Posokhova
authors.forename: Kirill A
authors.initials: KA
authors.lastname: Martemyanov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051245:Retinal Bipolar Cells / Q000378:metabolism* / Q000502:physiology; D012756:Sheep; D055366:Synaptic Potentials / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D011509:Proteoglycans; D018094:Receptors, Metabotropic Glutamate; D050053:TRPM Cation Channels; C116297:Trpm1 protein, mouse; C113897:metabotropic glutamate receptor 6; C560879:nyctalopin protein, mouse