Abolished interaction of NUB1 with mutant AIPL1 involved in Leber congenital amaurosis.

Leber congenital amaurosis (LCA) is often considered the most severe inherited retinopathy, and AIPL1 was the fourth gene identified as associated with LCA. Although the function of AIPL1 is unknown, it has been reported to interact with NUB1. Here, we searched for a NUB1-binding site on AIPL1 and located it between amino acid residues 181 and 330 in AIPL1. Importantly, many LCA-associated mutations of AIPL1 have been found at this site. Hence, we hypothesized that the interaction between NUB1 and AIPL1 is affected in patients with LCA. To test this possibility, we used three different assays to investigate the interaction between NUB1 and the AIPL1 mutants associated with LCA. Some of the AIPL1 mutants did not interact with NUB1, suggesting that abolishment of this interaction is involved in the pathogenesis of LCA. Other AIPL1 mutants, however, did interact with NUB1, suggesting that other molecules are also involved in the pathogenesis.