Nano-scale resolution of native retinal rod disk membranes reveals differences in lipid composition

J Cell Biol. 2021 Aug 2;220(8):e202101063. doi: 10.1083/jcb.202101063. Epub 2021 Jun 16.


Photoreceptors rely on distinct membrane compartments to support their specialized function. Unlike protein localization, identification of critical differences in membrane content has not yet been expanded to lipids, due to the difficulty of isolating domain-specific samples. We have overcome this by using SMA to coimmunopurify membrane proteins and their native lipids from two regions of photoreceptor ROS disks. Each sample's copurified lipids were subjected to untargeted lipidomic and fatty acid analysis. Extensive differences between center (rhodopsin) and rim (ABCA4 and PRPH2/ROM1) samples included a lower PC to PE ratio and increased LC- and VLC-PUFAs in the center relative to the rim region, which was enriched in shorter, saturated FAs. The comparatively few differences between the two rim samples likely reflect specific protein-lipid interactions. High-resolution profiling of the ROS disk lipid composition gives new insights into how intricate membrane structure and protein activity are balanced within the ROS, and provides a model for future studies of other complex cellular structures.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Alcohol Oxidoreductases / genetics
  • Alcohol Oxidoreductases / metabolism
  • Animals
  • Cattle
  • Cell Membrane / metabolism*
  • Cell Membrane / ultrastructure
  • Eye Proteins / immunology
  • Eye Proteins / metabolism*
  • Lipidomics
  • Membrane Lipids / metabolism*
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism*
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Microscopy, Electron, Transmission
  • Nanotechnology
  • Peripherins / metabolism
  • Retinal Rod Photoreceptor Cells / metabolism*
  • Retinal Rod Photoreceptor Cells / ultrastructure
  • Rhodopsin / metabolism
  • Single-Domain Antibodies / immunology
  • Tetraspanins / metabolism


  • ATP-Binding Cassette Transporters
  • Abca4 protein, mouse
  • Eye Proteins
  • Membrane Lipids
  • Membrane Proteins
  • Peripherins
  • Single-Domain Antibodies
  • Tetraspanins
  • Rhodopsin
  • Alcohol Oxidoreductases
  • Rdh8 protein, mouse