Nanoscale Architecture of the Rod Outer Segment

Article: Using cryo-electron tomography, UCI researchers reveal molecular mechanisms underlying mutations within the eye that lead to blindness
Source: University of California, Irvine, Medicine
Published: January 4, 2022



Scientists at University of California, Irvine, along with collaborators at the Max Planck Institute of Biochemistry have revealed the nanoscale molecular structure of key determinants of the mouse rod outer segment (ROS), the specialized sensory cilium of rod photoreceptor cells where phototransduction, the initial step of vision, takes place. The authors write, "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." Although the ultrastructure of the ROS had been described in previous years, the present study utilized cryo-electron tomography (cryo-ET) and a new sample preparation method to obtain molecular resolution images of the ROS. One of the authors explains, "Cryo-ET enabled us to image rim disc structures and to quantitatively assess the connectors between disks revealing the molecular landscape in ROS, including connectors between ROS disk membranes [and] address open questions regarding the close disk stacking and the high membrane curvature at disk rims." In particular, they report, "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." The study is especially relevant to retinal diseases such as retinitis pigmentosa and Stargardt disease that affect structural proteins. Based on the findings, they predict that new therapeutic approaches will likely emphasize gene-editing technologies over other interventions for retinal diseases.

My rating of this study: ⭐⭐⭐

Pöge M, Mahamid J, Imanishi SS, et al. "Determinants shaping the nanoscale architecture of the mouse rod outer segment." eLife.  10:e72817. 21 December 2021. https://doi.org/10.7554/eLife.72817