TY  - JOUR
A1  - Hanke-Gogokhia, Christin
A1  - Frederick, Jeanne M.
A1  - Zhang, Houbin
A1  - Baehr, Wolfgang
T1  - Binary Function of ARL3-GTP Revealed by Gene Knockouts
JF  - Retinal Degenerative Diseases : Mechanisms and Experimental Therapy
N2  - 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.
KW  - ARL3
KW  - ARL13b
KW  - PDE delta
KW  - UNC119
KW  - RP2
KW  - Photoreceptor
KW  - Germline knockout
KW  - Retina disease
Y1  - 2018
SN  - 978-3-319-75402-4
SN  - 978-3-319-75401-7
U6  - https://doi.org/10.1007/978-3-319-75402-4_39
SN  - 0065-2598
SN  - 2214-8019
VL  - 1074
SP  - 317
EP  - 325
PB  - Springer
CY  - Cham
ER  -