The GARP Domain of the Rod CNG Channel's ?1-Subunit Contains Distinct Sites for Outer Segment Targeting and Connecting to the Photoreceptor Disk Rim

Vision begins when light is captured by the outer segment organelle of photoreceptor cells in retina. Outer segments are modified cilia filled with hundreds flattened disk-shaped membranes. Disk membranes separated from surrounding plasma membrane, and each membrane type has unique protein components. The mechanisms underlying this sorting remain entirely unknown. In study, we investigated delivery rod cyclic nucleotide-gated (CNG) channel, which located where it mediates electrical response to light. Using Xenopus mouse models both sexes, now show that targeted CNG channel uses conventional secretory pathway, including processing ER Golgi, requires preassembly its constituent ?1 ?1 subunits. We further demonstrate N-terminal glutamic acid-rich (GARP) domain CNG?1 contains two distinct functional regions. region encodes specific information targeting segments. adjacent proline-enriched connects disk rims, likely through an interaction peripherin-2. These data reveal fine specializations within structural domains suggest sequestration SIGNIFICANCE STATEMENT Neurons other differentiated have a remarkable ability deliver organize signaling proteins at precise subcellular locations. report mediating photoreceptors, specialized regions N terminus ?-subunit: one responsible for ciliary another subsequent into membrane. findings expand our understanding molecular used neurons populate their critical compartments.