Abstract
The unique membrane organization of the rod outer segment (ROS), the specialized sensory cilium of rod photoreceptor cells, provides the foundation for phototransduction, the initial step in vision. ROS architecture is characterized by a stack of identically shaped and tightly packed membrane disks loaded with the visual receptor rhodopsin. A wide range of genetic aberrations have been reported to compromise ROS ultrastructure, impairing photoreceptor viability and function. Yet, the structural basis giving rise to the remarkably precise arrangement of ROS membrane stacks and the molecular mechanisms underlying genetically inherited diseases remain elusive. Here, cryo-electron tomography (cryo-ET) performed on native ROS at molecular resolution provides insights into key structural determinants of ROS membrane architecture. Our data confirm the existence of two previously observed molecular connectors/spacers which likely contribute to the nanometer-scale precise stacking of the ROS disks. We further provide evidence that the extreme radius of curvature at the disk rims is enforced by a continuous supramolecular assembly composed of peripherin-2 (PRPH2) and rod outer segment membrane protein 1 (ROM1) oligomers. We suggest that together these molecular assemblies constitute the structural basis of the highly specialized ROS functional architecture. Our Cryo-ET data provide novel quantitative and structural information on the molecular architecture in ROS and substantiate previous results on proposed mechanisms underlying pathologies of certain PRPH2 mutations leading to blindness.
Highlights
Rod photoreceptor cells are remarkably sensitive detectors for light
50% of the rod outer segment (ROS) disk membrane area is occupied by Rho (Palczewski, 2006)
It was previously suggested that the close proximity between disks is maintained by connectivity between the disk membranes, a model derived from 2D micrographs of metal stained, plastic embedded ROS sections showing zipper-like structures (Robertson, 1965)
Summary
Rod photoreceptor cells are remarkably sensitive detectors for light. Rho is a transmembrane G-protein coupled receptor that resides in a specialized cellular compartment in rods, the rod outer segment (ROS), which contains a stack of hundreds of identically shaped and precisely spaced membrane disks. The disk membranes are only interrupted by one or more clefts, so-called disk incisures (Makino et al, 2012). 50% of the ROS disk membrane area is occupied by Rho (Palczewski, 2006). The light sensitivity of rods relies on the elaborate ROS membrane architecture, which seemingly evolved to maximize the surface area of the membranes, thereby maximizing the amount of Rho for photon capture (Pugh and Lamb, 2000)
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