6 research outputs found
Q344ter Mutation Causes Mislocalization of Rhodopsin Molecules That Are Catalytically Active: A Mouse Model of Q344ter-Induced Retinal Degeneration
Q344ter is a naturally occurring rhodopsin mutation in humans that causes autosomal dominant retinal degeneration through mechanisms that are not fully understood, but are thought to involve an early termination that removed the trafficking signal, QVAPA, leading to its mislocalization in the rod photoreceptor cell. To better understand the disease mechanism(s), transgenic mice that express Q344ter were generated and crossed with rhodopsin knockout mice. Dark-reared Q344terrho+/β mice exhibited retinal degeneration, demonstrating that rhodopsin mislocalization caused photoreceptor cell death. This degeneration is exacerbated by light-exposure and is correlated with the activation of transducin as well as other G-protein signaling pathways. We observed numerous sub-micrometer sized vesicles in the inter-photoreceptor space of Q344terrho+/β and Q344terrhoβ/β retinas, similar to that seen in another rhodopsin mutant, P347S. Whereas light microscopy failed to reveal outer segment structures in Q344terrhoβ/β rods, shortened and disorganized rod outer segment structures were visible using electron microscopy. Thus, some Q344ter molecules trafficked to the outer segment and formed disc structures, albeit inefficiently, in the absence of full length wildtype rhodopsin. These findings helped to establish the in vivo role of the QVAPA domain as well as the pathways leading to Q344ter-induced retinal degeneration
The rapid and long-lasting growth of grasses following small falls of rain on stony downs in the arid interior of Australia
Surface electronic structure of the topological Kondo-insulator candidate correlated electron system SmB6
The response of Mitchell grasses (Astrebla spp.) and Button grass (Dactyloctenium radulans (R. Br.)) to rainfall and their importance to the survival of the Australian plague locust, Chortoicetes terminifera (Walker), in the arid zone
The structure of trp RNA-binding attenuation protein
The crystal structure of the trp RNA-binding attenuation protein of Bacillus subtilis solved at 1.8 Γ
resolution reveals a novel structural arrangement in which the eleven subunits are stabilized through eleven intersubunit Ξ²-sheets to form a Ξ²-wheel with a large central hole. The nature of the binding of L-tryptophan in clefts between adjacent Ξ²-sheets in the Ξ²-wheel suggests that this binding induces conformational changes in the flexible residues 25-33 and 49-52. It is argued that upon binding, the messenger RNA target forms a matching circle in which eleven U/GAG repeats are bound to the surface of the protein ondecamer modified by the binding of L-tryptophan