Date on Master's Thesis/Doctoral Dissertation
Biochemistry and Molecular Biology
Gregg, Ronald G.
Nyctalopin; Grm6; Bipolar cell; Retina; Trpm1 channel; Synaptogenesis
Vision disorders--Genetic aspects
Congenital stationary night blindness 1 (CSNBl) is a genetic disorder characterized in humans by night blindness, low visual acuity and myopia. CSNB 1 is caused by defects in genes that are involved in signaling between photoreceptors and depolarizing bipolar cells (DBCs). DBCs utilize a metabotropic glutamate receptor-6 (Grm6) cascade that modulates the activity of a non-specific cation channel. CSNBI is diagnosed by a reduced b-wave in the electroretinogram (ERG). A b-wave indicates that DBCs are depolarized in response to a flash of light. In the dark, there is a tonic release of glutamate from the photoreceptors into the synaptic cleft. This glutamate binds to the Grm6 receptor, activating a G-protein signal transduction cascade that closes a nonselective cation channel. The Gregg laboratory has identified this channel as the transient receptor potential melastatin l(Trpml) channel. The focus of my research is to determine how another protein, nyctalopin, which also lacks b-wave causes a loss of the channel's activity. Nyctalopin is an integral membrane protein with the entire leucine rich repeat in the extracellular space. Nyctalopin interacts directly with extracellular loops of Trpml. Although nyctalopin alone is not able to gate or traffic the Trpml channel to the membrane, gene expression profiling and membrane split ubiquitin yeast two hybrid screen suggest that a complex of proteins including nyctalopin are involved in either assembling or trafficking of the Trpm 1 channel to the plasma membrane.
Bojang, Pasano Pasano, "Topology and function of nyctalopin in yeast and in-vitro translation systems." (2010). Electronic Theses and Dissertations. Paper 124.