Molecular Bases of Disease
Deletion of both centrin 2 (CETN2) and CETN3 destabilizes the distal connecting cilium of mouse photoreceptors
Centrins (CETN1–4) are ubiquitous and conserved EF-hand–family Ca2+-binding proteins associated with the centrosome, basal body, and transition zone. Deletion of CETN1 or CETN2 in mice causes male infertility or dysosmia, respectively, without affecting photoreceptor function. However, it remains unclear to what extent centrins are redundant with each other in photoreceptors. Here, to explore centrin redundancy, we generated Cetn3GT/GT single-knockout and Cetn2−/−;Cetn3GT/GT double-knockout mice.The guanine nucleotide exchange factor Arf-like protein 13b is essential for assembly of the mouse photoreceptor transition zone and outer segment
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.
