Binary Function of ARL3-GTP Revealed by Gene Knockouts
- UNC119 and PDE delta are lipid-binding proteins and are thought to form diffusible complexes with transducin-alpha and prenylated OS proteins, respectively, to mediate their trafficking to photoreceptor outer segments. Here, we investigate mechanisms of trafficking which are controlled by Arf-like protein 3 (Arl3), a small GTPase. The activity of ARL3 is regulated by a GEF (ARL13b) and a GAP (RP2). In a mouse germline knockout of RP2, ARL3-GTP is abundant as its intrinsic GTPase activity is extremely low. High levels of ARL3-GTP impair binding and trafficking of cargo to the outer segment. Germline knockout of ARL3 is embryonically lethal generating a syndromic ciliopathy-like phenotype. Retina-and rod-specific knockout of ARL3 allow to determine the precise mechanisms leading to photoreceptor degeneration. The knockouts reveal binary functions of ARL3-GTP as a key molecule in late-stage photoreceptor ciliogenesis and cargo displacement factor.
| Author details: | Christin Hanke-GogokhiaORCiDGND, Jeanne M. Frederick, Houbin ZhangORCiD, Wolfgang BaehrORCiD |
|---|---|
| DOI: | https://doi.org/10.1007/978-3-319-75402-4_39 |
| ISBN: | 978-3-319-75402-4 |
| ISBN: | 978-3-319-75401-7 |
| ISSN: | 0065-2598 |
| ISSN: | 2214-8019 |
| Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/29721959 |
| Title of parent work (English): | Retinal Degenerative Diseases : Mechanisms and Experimental Therapy |
| Publisher: | Springer |
| Place of publishing: | Cham |
| Publication type: | Article |
| Language: | English |
| Date of first publication: | 2018/05/03 |
| Publication year: | 2018 |
| Release date: | 2022/03/17 |
| Tag: | ARL13b; ARL3; Germline knockout; PDE delta; Photoreceptor; RP2; Retina disease; UNC119 |
| Volume: | 1074 |
| Number of pages: | 9 |
| First page: | 317 |
| Last Page: | 325 |
| Funding institution: | National Eye InstituteUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Eye Institute (NEI) [EY08123, EY019298, EY014800-039003]; Research to Prevent BlindnessResearch to Prevent Blindness (RPB); Retina Research Foundation, Houston; Foundation for Retina Research; Nelson Trust |
| Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie und Biologie |
| DDC classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
| Peer review: | Referiert |
