Paired octamer rings of retinoschisin suggest a junctional model for cell-cell adhesion in the retina

Loss of retinoschisin (RS1)-mediated retinal cell-cell adhesion in the retina is the underlying cause of X-linked retinoschisis, leading to vision impairment in young males. Using cryo-electron microscopy, we show that RS1 forms paired back-to-back octameric rings. This molecular architecture provides a structural basis for understanding the disruptive effect of many disease-related mutants, because it localizes residues that are involved in the proper assembly of the oligomer. The back-to-back ring pairing is reminiscent of other junctional proteins, where multiple interactions between arrays of the same or similar proteins on two opposing membranes form a strong adhesion plaque.