Molecular basis for photoreceptor outer segment architecture

Abstract

To serve vision, vertebrate rod and cone photoreceptors must detect photons, convert the light stimuli into cellular signals, and then convey the encoded information to downstream neurons. Rods and cones are sensory neurons that each rely on specialized ciliary organelles to detect light. These organelles, called outer segments, possess elaborate architectures that include many hundreds of light-sensitive membranous disks arrayed one atop another in precise register. These stacked disks capture light and initiate the chain of molecular and cellular events that underlie normal vision. Outer segment organization is challenged by an inherently dynamic nature; these organelles are subject to a renewal process that replaces a significant fraction of their disks (up to ~10%) on a daily basis. In addition, a broad range of environmental and genetic insults can disrupt outer segment morphology to impair photoreceptor function and viability. In this chapter, we survey the major progress that has been made for understanding the molecular basis of outer segment architecture. We also discuss key aspects of organelle lipid and protein composition, and highlight distributions, interactions, and potential structural functions of key OS-resident molecules, including: kinesin-2, actin, RP1, prominin-1, protocadherin 21, peripherin-2/rds, rom-1, glutamic acid-rich proteins, and rhodopsin. Finally, we identify key knowledge gaps and challenges that remain for understanding how normal outer segment architecture is established and maintained.

Retinal energy demands control vascular supply of the retina in development and disease: The role of neuronal lipid and glucose metabolism

“…Photoreceptors (both rods and cones) have a unique mitochondrial localization and morphology (Winkler et al, 1997) with a high concentration of mitochondria in the ellipsoid region of the inner segment, near the ciliary junction to the outer segments (Goldberg et al, 2016). As noted, maintaining the sodium gradient in the photoreceptors is a crucial physiological feature that requires substantial energy derived from ATP hydrolysis (Hagins et al, 1970).…”

Adaptations in rod outer segment disc membranes in response to environmental lighting conditions

“…Rhodopsin is the light receptor in rod photoreceptor cells and is the predominant protein species in ROS discs. The light receptor is synthesized in the rod inner segment and transported to the base of the ROS, where it is incorporated into the membrane of newly synthesized ROS discs [8-12]. Rhodopsin initiates the first steps of vision via phototransduction by absorbing incoming photons and, upon photoactivation, binding and activating the heterotrimeric G protein transducin [13].…”

Structural and molecular bases of rod photoreceptor morphogenesis and disease

“…(Bales and Gross, 2015; Chan et al, 2016; Daiger et al, 2015; Fletcher et al, 2011; Flisikowska et al, 2014; Gorbatyuk and Gorbatyuk, 2013; Miyadera et al, 2012; Sahel et al, 2010; Siemiatkowska et al, 2014; Veleri et al, 2015; Wright et al, 2010). Recently, he molecular basis for rod cell function has been reviewed (Goldberg et al, 2016). …”