Purchase this article with an account.
V. Ramamurthy, F. van den Akker, J. Hurley; Molecular Basis of Leber Congenital Amaurosis Caused by Mutations in Aryl Hydrocarbon Receptor Interacting Protein Like-1 (AIPL1) . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3554.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Leber’s congenital amaurosis (LCA) is the most common form of inherited blindness at birth. LCA is usually inherited in autosomal recessive fashion. Mutations in six different retina specific genes have been linked to LCA in humans. Recently, several mutations in a novel gene, AIPL1, have been linked to LCA. The aim of this study is to understand the molecular basis of LCA caused by mutations in AIPL1 and to elucidate the normal function of AIPL1. Methods:Proteins that interact with AIPL1 were isolated by yeast-two hybrid analysis using human AIPL1 as bait and bovine retinal cDNA prey library. The interaction was further confirmed using in vitro binding assay. Proteins that were isolated by yeast two hybrid analysis were also tested for their ability to interact with various homozygous mutants in AIPL1 that are linked to LCA in humans. Results:Of approximately 2.5 x 106 colonies screened, we identified 34 clones that interacted with AIPL1. These 34 clones represent 8 different proteins. Six of the eight AIPL1 targets (32 clones) identified by the screen encode proteins with a C-terminal prenylation motif. Both our yeast two hybrid analysis and in vitro binding studies confirm that AIPL1 specifically interacts with farnesylated proteins. Homozygous mutations in AIPL1 linked to LCA prevent AIPL1 from interacting with farnesylated proteins. Conclusions:Our study identified a biochemical activity of AIPL1 that is linked to LCA. This study defines a novel interaction between AIPL1 and farnesylated proteins. Mutations in AIPL1 that are linked to LCA abolish its ability to bind farnesylated proteins without compromising the stability of AIPL1. Our study suggests that the critical function of AIPL1 within the photoreceptors requires interactions with farnesylated proteins.
This PDF is available to Subscribers Only