Molecular complexes that direct rhodopsin transport to primary cilia

Abstract

Rhodopsin is a key molecular constituent of photoreceptor cells, yet understanding of how it regulates photoreceptor membrane trafficking and biogenesis of light-sensing organelles, the rod outer segments (ROS) is only beginning to emerge. Recently identified sequence of well-orchestrated molecular interactions of rhodopsin with the functional networks of Arf and Rab GTPases at multiple stages of intracellular targeting fits well into the complex framework of the biogenesis and maintenance of primary cilia, of which the ROS is one example. This review will discuss the latest progress in dissecting the molecular complexes that coordinate rhodopsin incorporation into ciliary-targeted carriers with the recruitment and activation of membrane tethering complexes and regulators of fusion with the periciliary plasma membrane. In addition to revealing the fundamental principals of ciliary membrane renewal, recent advances also provide molecular insight into the ways by which disruptions of the exquisitely orchestrated interactions lead to cilia dysfunction and result in human retinal dystrophies and syndromic diseases that affect multiple organs, including the eyes.

Keywords: ADRP; Arfs; Autosomal Dominant Retinitis Pigmentosa; BBS; BBSome; Bardet-Biedl Syndrome; CTS; Ciliary Targeting Signal; Cilium; DHA; Docosahexaenoic Acid; GAP; GC1; GEF; GTPase Activating Protein; Guanine Nucleotide Exchange Factor; Guanylyl Cyclase 1; IFT; Intraflagellar Transport; JBTS; Joubert Syndrome; MKS; MT; MTOC; Meckel Syndrome; Microtubule Organizing Center; Microtubules; NPHP; Nephronophthisis; OCT; Optical Coherence Tomography; PLA; Proximity Ligation Assay; RIS; ROS; RPGR; RTC(s); Rabs; Retinitis Pigmentosa GTPase Regulator; Rhodopsin; Rhodopsin Transport Carrier(s); Rod Inner Segment(s); Rod Outer Segment(s); SNARE; Soluble N-ethylmaleimide-sensitive Factor Attachment Protein Receptor; TGN; Trafficking; Trans-Golgi Network; a conserved complex of BBS proteins.