Mechanistic Insights into MYO1C-Mediated Rhodopsin Trafficking and Rod Photoreceptor Homeostasis.

Rhodopsin trafficking from the photoreceptor inner segment to the outer segment is essential for proper photoreceptor function. MYO1C, an actin-based motor protein, is believed to play a role in this process, but the exact mechanism is not fully understood. Researchers investigated MYO1C's role in rhodopsin trafficking and rod photoreceptor cell homeostasis.

In-silico docking suggested a possible interaction between MYO1C's C-terminal region and rhodopsin's VxPx ciliary trafficking motif. Biochemical tests confirmed that full-length MYO1C interacts with rhodopsin, but when the C-terminal domain was deleted, this interaction was lost. Using live-cell imaging and fluorescence recovery after photobleaching in hTERT-RPE1 cells, the study found that MYO1C's C-terminal region is necessary for efficient rhodopsin trafficking, membrane localization, and ciliary targeting.

In native murine rod photoreceptors, MYO1C was present on both inner and outer segments. However, mice lacking Myo1c globally experienced age-dependent rhodopsin mislocalization, apo-opsin accumulation, and progressive retinal dysfunction, starting at 6 months old. Photopic responses remained relatively stable. Rod-specific Myo1c deletion also led to progressive scotopic dysfunction and reduced a-wave recovery after light stimulation.

In contrast, cone-specific Myo1c deletion did not affect photopic function. These findings establish MYO1C as a crucial regulator of rhodopsin trafficking and demonstrate its preferential, cell-autonomous requirement for maintaining rod photoreceptor homeostasis and phototransduction recovery.