The Leber congenital amaurosis gene product AIPL1 is localized exclusively in rod photoreceptors of the adult human retina

Abstract

Leber congenital amaurosis (LCA) is the most severe inherited retinal dystrophy resulting in markedly impaired vision or blindness at birth. LCA is characterized by an extinguished electroretinogram in infancy, which is thought to be indicative of an early and severe impairment of both the rod and cone photoreceptors in the human retina. Recently, the aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) gene was identified as the fourth causative gene of LCA. AIPL1 encodes a 384 amino acid protein of unknown function. We have generated a polyclonal antibody against a peptide from a unique region within the primate AIPL1 protein, which detects a protein of approximately 43 kDa in human retinal extracts. 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). Within the retina, AIPL1 was detected only in the rod photoreceptor cells of the peripheral and central human retina. The AIPL1 staining pattern extended within the rod photoreceptor cells from the inner segments, through the rod nuclei to the rod photoreceptor synaptic spherules in the outer plexiform layer. AIPL1 was not detected in the cone photoreceptors of peripheral or central human retina. This study is the first to suggest that AIPL1 performs a function essential to the maintenance of rod photoreceptor function.

The inherited blindness associated protein AIPL1 interacts with the cell cycle regulator protein NUB1

“…By immunohistochemistal studies, we demonstrated that the immunoreactive AIPL1 is present in both the developing and mature photoreceptors of the retina and that its subcellular localization overlaps with that of NUB1. The immunolocalization within the adult retina identified here is consistent with the recent results of van der Spuy et al (21), who demonstrate that AIPL1 localizes to both the cytoplasm and the nucleus of the photoreceptor cells of the retina, and E. Deery et al (manuscript in preparation), who also observe localization of the protein in the nucleus and cytoplasm of cultured mammalian cells. Moreover, the high perinuclear concentration of AIPL1 in the differentiated retina suggests that it may function similarly to AIP, in cytoplasmic stability and trafficking its target, such as NUB1, to the nucleus (7)(8)(9)(10)(11)(12)(13)(14)(15).…”

Interaction of Aryl Hydrocarbon Receptor-interacting Protein-like 1 with the Farnesyl Moiety

“…AIPL1 is expressed selectively in the retina and the pineal gland (3,5). AIPL1 shares high sequence homology (49% identity) and similar domain organization with the ubiquitously expressed aryl hydrocarbon receptor-interacting protein (AIP) (3).…”

Evaluation of Italian Patients with Leber Congenital Amaurosis due to AIPL1 Mutations Highlights the Potential Applicability of Gene Therapy

“…AIPL1 expression has been detected in both rods and cones during retinal development while in the differentiated retina expression seems restricted to rod photoreceptors. 13,14 Although it has been hypothesized that AIPL1 expression in cones is restricted to the retinal developmental period, very recent findings have shown that AIPL1 is expressed in human adult cones, where it may function to preserve cone activity and survival. 15 Successful AIPL1 retinal gene transfer using adeno-associated viral (AAV) vectors has been achieved in two different AIPL1 mouse models, 16,17 suggesting that this strategy can be potentially applied to LCA4 patients.…”