These results are consistent with the proposal that XRPGR is important in the function of a single microtubular organelle, the paired centrioles or basal bodies, and the associated transitional zone of sensory and motile cilia.
32 The distinctive roles of the XRPGR
ex1–19 and XRPGR
ORF15 remain unclear: only RPGR
ex1–19 was detected in motile cilia of mouse trachea, but both isoforms were present in connecting cilia.
25 The functions of primary (nonmotile) cilia are not fully elucidated, but there is increasing evidence that, as with sensory cilia, they also act as sensory organelles (with the exception of nodal cilia, which influence left-right asymmetry).
40 41 Primary cilia are present in virtually all cells, but are transiently lost (deciliated) when the centrioles separate during mitosis, to be reassembled in the G1 phase.
41 In early
X. laevis development, XRPGR expression, detectable by RT-PCR, may reflect its association with such primary cilia, from fertilization through cleavage and subsequent embryonic stages. In whole-mount embryos, higher-level expression of XRPGR, first detectable in the anterior neural plate and developing optic vesicle, is increasingly localized to the eye. Its presence in the eye was associated with expression in all three neuronal layers of the retina, although in adult
X. laevis retina, it was most evident in the rod and cone photoreceptors. Here, XRPGR localized to the axoneme of the connecting cilium, which, although similar to a primary cilium, appears to be an extended transitional zone. In motile cilia, the transitional zone lies between the distal axoneme (containing nine peripheral and one central microtubular doublets) and the basal body (containing nine microtubular triplets and no central doublet).
25 42 The transitional zone contains microtubules that are less stable than in the outer axonemal or basal body regions and is the site where deciliation normally occurs, by disorganization of microtubules and constriction of the ciliary membrane,
43 44 perhaps suggesting a vulnerability that may be important in RPGR-related retinal degenerations. This would be consistent with the observation that in XLRP, the connecting cilia of rods and cones are initially structurally normal,
45 indicating a more specialized function than maintenance of ciliary structure.