New Insight into Inherited Blindness: Analysis of the role of RAB28

New findings from the Blacque lab, published in PLoS Genetics [1],provides new insight into the function of a very poorly characterised Rab GTPase protein linked to a form of inherited blindness called cone-rod dystrophy. Using C. elegans roundworms, they report that rab-28 is expressed only in ciliated sensory neurons and encodes a protein that specifically localises to the hair-like cilium that extends from the surface of most metazoan cells. Within the cilium, RAB-28 hitches a ride with a microtubule-based transport system called IFT, or intraflagellar transport, which builds and maintains all eukaryotic cilia and flagella. They also found that the ciliary and IFT association of RAB-28 depends on its nucleotide-bound state, as well as the BBSome, which is a ciliary disease-associated complex that acts as a cargo adaptor for IFT trains. Furthermore, the new data suggests that cilium-associated RAB-28 influences the functions of a neighbouring non-ciliated glial cell, suggesting that the GTPase may regulate poorly understood intercellular signaling events during sensory pore development and morphogenesis. Commenting on the study, SBBS graduate student Stephen Carter and co-first author on the study remarked: “the new data provides the first in-depth molecular analysis of ciliary RAB28 in any system and provides a platform for further dissecting the role of small GTPases in cilium biology and disease”. For the remainder of his PhD research, and together with his co-supervisor, Assoc. Prof. Breandan Kennedy, Stephen is developing zebrafish models to investigate vertebrate RAB28 function and determine the extent of RAB28 functional conservation between worms and fish.

Jensen, V.L., et al., Whole-Organism Developmental Expression Profiling Identifies RAB-28 as a Novel Ciliary GTPase Associated with the BBSome and Intraflagellar Transport. PLoS Genet, 2016. 12(12): p. e1006469.