Disease relevance of AIPL1

• Therefore, it is possible that the early-onset form of retinal degeneration seen in LCA patients with AIPL1 mutations may be due to a defect in the regulation of cell cycle progression during photoreceptor maturation [1].
• The AIPL1-NUB1 interaction was verified by co-immunoprecipitation studies in Y79 retinoblastoma cells, demonstrating that this interaction occurs within cells that share a number of features with retinal progenitor cells [1].
• Younger patients with an AIPL1 or RPGRIP1 variation were found to have severely reduced vision [2].
• CONCLUSIONS: The phenotype of LCA in patients with AIPL1 mutations is relatively severe, with a maculopathy in most patients and keratoconus and cataract in a large subset [3].
• AIPL1, a protein implicated in Leber's congenital amaurosis, interacts with and aids in processing of farnesylated proteins [4].

High impact information on AIPL1

• AIPL1 mutations may cause approximately 20% of recessive LCA, as disease-causing mutations were identified in 3 of 14 LCA families not tested previously for linkage [5].
• Mutations in AIPL1 cause Leber congenital amaurosis, a severe early-onset retinopathy that leads to visual impairment in infants [6].
• Before any noticeable pathology, there was a reduction in the level of rod cGMP phosphodiesterase (PDE) proportional to the decrease in AIPL1 expression, whereas other photoreceptor proteins were unaffected [6].
• Thus loss of AIPL1 would result in a condition that phenocopies retinal degenerations in the rd mouse and in a subgroup of human patients [6].
• Analysis of isoprenylation in cultured human cells shows that AIPL1 enhances the processing of farnesylated proteins [4].

Biological context of AIPL1

• These data show that AIPL1 can modulate protein translocation and act in a chaperone-like manner and suggest that AIPL1 is an important modulator of NUB1 cellular function [7].
• The phenotype of Leber congenital amaurosis in patients with AIPL1 mutations [3].
• One form of LCA, LCA4, maps to chromosome 17p13 and is genetically distinct from other forms of LCA [8].
• Therefore, AIPL1 directly or indirectly affects more than one component of phototransduction [9].
• RESULTS: Five single nucleotide polymorphisms in AIPL1, RPGRIP1, and GUCY2D were detected in the proband by microarray screening, and all were validated by direct sequencing [10].

Anatomical context of AIPL1

• These data raise the possibility that AIPL1 is important for appropriate photoreceptor formation during development and/or survival following differentiation [1].
• Co-transfection of AIPL1 with GFP-NUB1-N and GFP-NUB1-C resulted in an AIPL1-dependent suppression of GFP-NUB1-N perinuclear inclusions and GFP-NUB1-C intranuclear inclusions leading to the redistribution of these fragments in the cytoplasm [7].
• AIPL1 was not detected in the cone photoreceptors of peripheral or central human retina [11].
• Within the retina, AIPL1 was detected only in the rod photoreceptor cells of the peripheral and central human retina [11].
• A screen of human tissues and immortalized cell lines with this antibody reveals AIPL1 to be specific to human retina and cell lines of retinal origin (Y79 retinoblastoma cells) [11].

Associations of AIPL1 with chemical compounds

• We found a homozygous nonsense mutation in the AIPL1 gene, which replaces a tryptophan with a stop codon (Trp278X) [12].

Physical interactions of AIPL1

• AIPL1 interacts with the cell cycle regulator NEDD8 ultimate buster protein 1 (NUB1) [7].

Regulatory relationships of AIPL1

• Interestingly, AIPL1 was able to act in a chaperone-like fashion to efficiently suppress inclusion formation by NUB1 fragments [7].

Other interactions of AIPL1

• We examined the effect of a range of pathogenic and engineered mutations on the ability of AIPL1 to modulate NUB1 localization or inclusion formation [7].
• We also identified affected individuals in two apparently dominant families, diagnosed with juvenile retinitis pigmentosa or dominant cone-rod dystrophy, respectively, who are heterozygous for a 12-bp AIPL1 deletion [8].
• The present study establishes a genotype-phenotype correlation for AIPL1, CRB1, and GUCY2D [13].
• The frequency of RPE65 mutations was 9.5%; and of AIPL1 mutations 4.8% [14].
• Role of AIP and its homologue the blindness-associated protein AIPL1 in regulating client protein nuclear translocation [15].

Analytical, diagnostic and therapeutic context of AIPL1

• When eukaryotic cells were transfected with the AIPL1 expression constructs, we show by immunofluorescence microscopy that wild-type protein is distributed throughout the nucleus and cytoplasm [16].
• Immunofluorescence confocal microscopy was used to examine the coexpression of AIPL1 with the long/medium (L/M) and short (S) wavelength-sensitive cone photoreceptors in the developing human retina [17].
• METHODS: A comprehensive spatiotemporal examination of AIPL1 distribution during development was performed by immunohistochemistry, using a previously characterized AIPL1 anti-serum [17].

References