マウス杆体光受容体における視細胞外節伸長に必要とされるロドプシンの組み立てコアの標的指向性送達

Vertebrate vision in dim-light environments is initiated by rod photoreceptor cells that express the photopigment rhodopsin, a G protein-coupled receptor (GPCR). To ensure efficient light capture, rhodopsin is densely packed into hundreds of tightly stacked membrane discs within the rod-shaped outer segment compartment. Along with its role in eliciting the visual response, rhodopsin serves as a building block necessary for proper outer segment formation and a trafficking guide for a few outer segment resident membrane proteins. An interesting aspect of rod homeostasis is that mutations that affect the localization of rhodopsin to the outer segment result in photoreceptor degeneration. In this study, we focus on determining the properties of rhodopsin's cytosolic C-terminus required for either proper outer segment trafficking or the capacity to extend the rudimentary outer segment in rhodopsin knockout (RhoKO) rods. We find that the well-described C-terminal QVAPA outer segment targeting motif also plays a role in endoplasmic reticulum (ER) exit and is necessary for elongation of the outer segment compartment. We identify that rhodopsin's core, helix-8, CC anchor, and QVAPA targeting motif are the minimal requirements to extend the rudimentary outer segment in RhoKO rods. Our findings provide useful insights into rhodopsin's molecular features needed for outer segment delivery and subsequent elongation of this membrane-rich compartment.