Arf GTPases are crucial for intracellular membrane trafficking to and from the Golgi, but the upstream activation of Arfs remains unclear. In photoreceptor cells, Arf4 is involved in the transport of rhodopsin to the primary cilia, and mutations in this trafficking pathway give rise to the blinding disease autosomal dominant retinitis pigmentosa (ADRP). Because the Arf guanine nucleotide exchange factor (GEF) GBF1 is a candidate for Arf4 activation in HeLa cells, in this issue (p. 3975), Dusanka Deretic and co-workers examine the role of GBF1 in Arf4 activation in frog retina photoreceptor cells. They show that GBF1 localises to the trans-Golgi network (TGN), where it directly interacts with Arf4 and with newly synthesised rhodopsin through its N-terminal DCB-HUS domain. Indeed, blockade of rhodopsin transit through the Golgi by using cycloheximide abolished any interactions between GBF1, Arf4 and rhodopsin, highlighting the requirement of cargo influx. Moreover, the ternary complex is sensitive to the GBF1 inhibitor Golgicide A, further indicating that the functional complex is formed at the Golgi/TGN. The authors suggest that this means of ciliary transport represents an adaptation in photoreceptor cells, enabling them to manage their large amount of rhodopsin-containing membranes by concentrating GBF1 at Golgi exit sites where it senses the emerging cargo, and also recruits and activates the transport factor Arf4 for delivery to the primary cilium.
