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  - 
TY  - JOUR
A1  - Hanke-Gogokhia, Christin
A1  - Zhang, Houbin
A1  - Frederick, Jeanne M.
A1  - Baehr, Wolfgang
ED  - Rickman, CB
ED  - LaVail, MM
ED  - Anderson, RE
ED  - Grimm, C
ED  - Hollyfield, J
ED  - Ash, J
T1  - The Function of Arf-like Proteins ARL2 and ARL3 in Photoreceptors
JF  - Retinal Degenerative Diseases : Mechanisms and Experimental Therapy
N2  - Arf-like proteins (ARLs) are ubiquitously expressed small G proteins of the RAS superfamily. In photoreceptors, ARL2 and ARL3 participate in the trafficking of lipidated membrane-associated proteins and colocalize in the inner segment with UNC119A and PDE delta. UNC119A and PDE delta are acyl-and prenyl-binding proteins, respectively, involved in trafficking of acylated (transducin-alpha subunit, nephrocystin NPHP3) and prenylated proteins (GRK1, PDE6). Germline Arl3 knockout mice do not survive beyond postnatal day 21 and display ciliary defects in multiple organs (kidney, liver and pancreas) as well as retinal degeneration. Conditional knockouts will be necessary to delineate mechanisms of protein transport in retina disease.
KW  - Arf-like protein 3 (ARL3)
KW  - Arf-like protein 2 (ARL2)
KW  - Phosphodiesterase delta-subunit (PDE delta)
KW  - unc-119 homolog (C. elegans) (UNC119A)
KW  - Retinitis pigmentosa protein 2 (RP2)
KW  - Rod photoreceptor
Y1  - 2016
SN  - 978-3-319-17121-0; 978-3-319-17120-3
U6  - https://doi.org/10.1007/978-3-319-17121-0_87
SN  - 0065-2598
VL  - 854
SP  - 655
EP  - 661
PB  - Springer International Publishing AG
CY  - Cham
ER  -