TY  - JOUR
A1  - Hanke-Gogokhia, Christin
A1  - Wu, Zhijian
A1  - Gerstner, Cecilia D.
A1  - Frederick, Jeanne M.
A1  - Zhang, Houbin
A1  - Baehr, Wolfgang
T1  - Arf-like Protein 3 (ARL3) Regulates Protein Trafficking and Ciliogenesis in Mouse Photoreceptors
JF  - The journal of biological chemistry
N2  - Arf-like protein 3 (ARL3) is a ubiquitous small GTPase expressed in ciliated cells of plants and animals. Germline deletion of Arl3 in mice causes multiorgan ciliopathy reminiscent of Bardet-Biedl or Joubert syndromes. As photoreceptors are elegantly compartmentalized and have cilia, we probed the function of ARL3 (ADP-ribosylation factor (Arf)-like 3 protein) by generating rod photoreceptor-specific (prefix (rod)) and retina-specific (prefix (ret)) Arl3 deletions. In predegenerate (rod)Arl3(-/-) mice, lipidated phototransduction proteins showed trafficking deficiencies, consistent with the role of ARL3 as a cargo displacement factor for lipid-binding proteins. By contrast, (ret)Arl3(-/-) rods and cones expressing Cre recombinase during embryonic development formed neither connecting cilia nor outer segments and degenerated rapidly. Absence of cilia infers participation of ARL3 in ciliogenesis and axoneme formation. Ciliogenesis was rescued, and degeneration was reversed in part by subretinal injection of adeno-associated virus particles expressing ARL3-EGFP. The conditional knock-out phenotypes permitted identification of two ARL3 functions, both in the GTP-bound form as follows: one as a regulator of intraflagellar transport participating in photoreceptor ciliogenesis and the other as a cargo displacement factor transporting lipidated protein to the outer segment. Surprisingly, a farnesylated inositol polyphosphate phosphatase only trafficked from the endoplasmic reticulum to the Golgi, thereby excluding it from a role in photoreceptor cilia physiology.
KW  - animal model
KW  - gene knock-out
KW  - lipid-binding protein
KW  - photoreceptor
KW  - protein trafficking (Golgi)
KW  - retinal degeneration
Y1  - 2016
U6  - https://doi.org/10.1074/jbc.M115.710954
SN  - 0021-9258
SN  - 1083-351X
VL  - 291
SP  - 7142
EP  - 7155
PB  - American Society for Biochemistry and Molecular Biology
CY  - Bethesda
ER  -