AIPL1, a protein implicated in Leber's congenital amaurosis, interacts with and aids in processing of farnesylated proteins

被引：60

作者：

Ramamurthy, V

Roberts, MA

van den Akker, F

Niemi, G

Reh, TA

Hurley, JB ^{[1
]}

机构：

[1] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[2] Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA

[3] Cleveland Clin Fdn, Lerner Res Inst, Ctr Struct Biol, Cleveland, OH 44195 USA

[4] Cleveland Clin Fdn, Dept Mol Biol, Cleveland, OH 44195 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2003年 / 100卷 / 22期

关键词：

D O I：

10.1073/pnas.2134194100

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The most common form of blindness at birth, Leber's congenital amaurosis (LCA), is inherited in an autosomal recessive fashion. Mutations in six different retina-specific genes, including a recently discovered gene, AIPL1, have been linked to LCA in humans. To understand the molecular basis of LCA caused by aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) mutations, and to elucidate the normal function of AIPL1, we performed a yeast two-hybrid screen using AIPL1 as bait. The screen demonstrated that AIPL1 interacts specifically with farnesylated proteins. Mutations in AIPL1 linked to LCA compromise this activity. These findings suggest that the essential function of AIPL1 within photoreceptors requires interactions with farnesylated proteins. Analysis of isoprenylation in cultured human cells shows that AIPL1 enhances the processing of farnesylated proteins. Based on these findings, we propose that AIPL1 interacts with farnesylated proteins and plays an essential role in processing of farnesylated proteins in retina.

引用

页码：12630 / 12635

页数：6