Aipl1 Lca4

AIPL1 (aryl-hydrocarbon interacting proteinlike 1), described by Sohocki et al. [123], was the fourth of the LCA genes to be identified and accounts for 3.4-11% [24, 48, 66, 124] of cases. It has also been identified as putatively causative in autosomal dominant cone-rod dystrophy and retinitis pigmentosa (RP) [124] ( aipl1mut.htm), though Cremers [18] has expressed some doubt about this.

The AIPL1 gene (located on 17p13.2) encodes a 384-aminoacid protein that contains three tetratricopeptide (TPR) motifs. TPR domains are sites of protein-protein interaction, and it is thought that the AIPL1 protein, through this motif, interacts and aids in the processing of farnesylated proteins [151] which are responsible for attachment to cell membranes, in other words, maintaining photoreceptor architecture.

AIPL1 has also been shown to interact with NEDD8 ultimate buster-1 (NUB1), which is an interferon inducible protein; both NUB1 and

AIPL1 are expressed within the developing cone and rod photoreceptors but co-localise solely within the rods of the mature retina [2,123,139]. This suggests that AIPL1 is essential for the normal development of photoreceptor cells. NUB1 is located predominantly within the nuclear component of cells as compared to AIPLi,which is largely cytoplasmic [137,139]. It has now been shown that AIPL1 can modulate protein translocation through enhanced farnesylation, and acts in a chaperone-like manner escorting prenylated proteins to their target membranes, suggesting that AIPL1 is an important modulator of NUBi cellular function [138]. AIPLi mutations implicated in LCA have been shown in vitro not to interact with NUB1 suggesting that this lack of interaction may be a key factor in the abnormal retinal function seen in the LCA retina [59].

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