Functional Study Of ARL2 In Mammalian Photoreceptors

Eye,is an organ for visual formation The most critical part of eye for light perception is retina,which contains light sensitive photoreceptors.Structurally,photoreceptor cells consist of outer segments and inner segments that are joined by connecting cilium.There are two major types photoreceptor cells in mammalian retina,including rod and cone photoreceptors,which are responsible for photopic and scotopic vision,respectively.Rhodopsin,found in rods,is synthesized in the inner segment of photoreceptor cells and transported to the outer segment.This transport process is regulated by a variety of protein factors.Existing evidence suggest that ARL2(ADP ribosylation factor-like protein 2)could be one of these factors.ARL2 is encoded by the Arl2 gene and has a molecular weight of around 20 KDa.ARL2 is a GTPase capable of binding and hydrolyzing GTP Prior studies suggest that ARL2 is involved in the folding of tubulin subunits,as well as in the assembly and disassembly of heterodimeric proteins,which also regulates the integrity of microtubules.Additionally,ARL2 was shown to be localized in the retinal photoreceptor cells,but its specific role and function have not been elucidated so far.In this paper,the in vivo and in vitro experiments were carried out by generation and characterization of the Arl2 gene retina-specific knockout mouse model,as well as investigation of microtubule network in cultured cells overexpression wild type and mutant ARL2.The results show that overexpression of the Arl2 gene and its mutants caused the collapse of the microtubule network structure of the transfected cells and abolished the formation of cilia.In the Arl2 transgenic knockout mouse model,ARL2 deletion caused a decrease in assembly of tubulin ?/?-tubulin heterodimer,increased depolymerization,and impediment to microtubule formation,resulting in the abnormal photoreceptor morphology.The absence of ARL2 directly affects the transport of the light signal transduction protein IFT,leading to defective photoreceptor segment,and the retinal function is impaired.In summary,ARL2 is critical for the morphology and function of the photoreceptor by maintaining the stability of tubulin synthesis and the dynamic balance of microtubule dynamics.The study of ARL2 in the retina has insightful information for pathogenesis of Retinitis pigmentosa.