Arf-like Protein 3 (ARL3) Regulates Protein Trafficking and Ciliogenesis in Mouse Photoreceptors

Abstract

Arf-like protein 3 (ARL3) is a ubiquitous small

Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport

“…This localisation is similar to that of the mammalian protein implicated in retinitis pigmentosa, and is consistent with the suggested role of FAM161b in cargo delivery to photoreceptor outer segments (cilia) [60,61]. Both GFP reporters for RAB-28 (driven by bbs-8 gene or endogenous promoter), the orthologue of the small ciliary GTPase RAB28 linked to human autosomal-recessive cone-rod dystrophy [62–64], localise along the entire cilium. (Fig 2 and Fig 3A).…”

“…elegans ciliary proteins we identified, we sought to characterise RAB-28 further for the following reasons: (1) human RAB28 is associated with a possible ciliopathy (cone-rod dystrophy [62,63]), (2) many small GTPases play essential roles in ciliogenesis and ciliary membrane trafficking pathways [10], and (3) aside from reports of RAB28 localising at the basal body [62] or the cilium [64], there is a complete absence of molecular studies on this evolutionarily conserved protein that support a functional and mechanistic link to cilia.…”

“…Although recent studies show that mammalian RAB28 is localised to the mammalian photoreceptor basal body and cilium [62,64], its role in photoreceptors and in other tissues and organisms remains unknown. Here, we show that C .…”

Gates for soluble and membrane proteins, and two trafficking systems (IFT and LIFT), establish a dynamic ciliary signaling compartment

“…We propose the name Lipidated protein Intraflagellar Targeting (LIFT) to describe its specific trafficking functions and apparent functional association with IFT, as described below (Figure 2). LIFT uses two homologous proteins, PDE6D or UNC119B, to target proteins with lipid anchors to the ciliary membrane [59 , [60][61][62][63][64][65][66]. The carrier proteins have a hydrophobic pocket that solubilizes cargo by sheltering their newly-lipidated chains [62,65].…”

Sorting of lipidated cargo by the Arl2/Arl3 system

“…29 Recently Arl3 was shown to regulate trafficking of prenylated proteins in photoreceptors and a photoreceptor specific knockout of Arl3 causes severe defects in photoreceptor function and structure, in line with the recent identification of an Arl3 mutant in retinitis pigmentosa. [30][31][32] The cargo carriers PDE6d and Unc119…”