| First Author | Hanke-Gogokhia C | Year | 2017 |
| Journal | J Biol Chem | Volume | 292 |
| Issue | 52 | Pages | 21442-21456 |
| PubMed ID | 29089384 | Mgi Jnum | J:256778 |
| Mgi Id | MGI:6107806 | Doi | 10.1074/jbc.RA117.000141 |
| Citation | Hanke-Gogokhia C, et al. (2017) The guanine nucleotide exchange factor Arf-like protein 13b is essential for assembly of the mouse photoreceptor transition zone and outer segment. J Biol Chem 292(52):21442-21456 |
| abstractText | Arf-like protein 13b (ARL13b) is a small GTPase that functions as a guanosine nucleotide exchange factor (GEF) for ARL3-GDP. ARL13b is located exclusively in photoreceptor outer segments (OS) presumably anchored to discs by palmitoylation, whereas ARL3 is an inner segment cytoplasmic protein. Hypomorphic mutations affecting the ARL13b G-domain inactivate GEF activity and lead to Joubert syndrome (JS) in humans. However, the molecular mechanisms in ARL13b mutation-induced Joubert syndrome, particularly the function of primary cilia, are still incompletely understood. Because Arl13b germline knockouts in mouse are lethal, we generated retina-specific deletions of ARL13b in which ARL3-GTP formation is impaired. In mouse (ret)Arl13b(-/-) central retina at postnatal day 6 (P6) and older, outer segments were absent, thereby preventing trafficking of outer segment proteins to their destination. Ultrastructure of postnatal day 10 (P10) central (ret)Arl13b(-/-) photoreceptors revealed docking of basal bodies to cell membranes, but mature transition zones and disc structures were absent. Deletion of ARL13b in adult mice via tamoxifen-induced Cre/loxP recombination indicated that axonemes gradually shorten and outer segments progressively degenerate. IFT88, essential for anterograde intraflagellar transport (IFT), was significantly reduced at (tam)Arl13b(-/-) basal bodies, suggesting impairment of intraflagellar transport. AAV2/8 vector-mediated ARL13b expression in the (ret)Arl13b(-/-) retina rescued ciliogenesis. |
