Date on Master's Thesis/Doctoral Dissertation
Biochemistry and Molecular Biology
Gregg, Ronald G.
Night vision--Genetic aspects; Vision disorders--Genetic aspects
Mutations in the NYX gene, encoding the novel protein nyctalopin, cause human congenital stationary night blindness type 1 (CSNB1). CSNB1 is an X-linked recessive condition and is identified by a loss of the electroretinogram (ERG) b-wave while the a-wave remains intact (Miyake et al., 1986). The b-wave in normal patients is generated by the depolarization of one class of bipolar cells, which receive signals from the photoreceptors. This indicates that CSNB1 is a loss of signaling from the photo receptors to the depolarizing bipolar cells. Normal stimulation of photoreceptors by light causes the photoreceptors to hyperpolarize and reduce the amount of neurotransmitter, glutamate, released into the synaptic cleft. The decrease in glutamate causes Grm6, a metabotropic glutamate receptor, at the postsynaptic depolarizing bipolar cell dendrites to reduce its activity. This signal is relayed by a second messenger system to result in the opening of a non-selective cation channel, which depolarizes one class of bipolar cells. The signaling to the non-selective cation channel in depolarizing bipolar cells is disrupted when nyctalopin is absent. Recent data shows that the non-selective cation channel is the transient receptor potential subfamily M member 1 (TRPM1) channel (Shen et al., 2009; Morgans et al., 2009; Koike et al., 2009). The focus of my studies has been to understand the function of nyctalopin in the depolarizing bipolar cells. I characterized TRPM1 expression in the retina, investigated the interdependence between nyctalopin, Grm6 and TRPM1 and determined the interactions between nyctalopin and Grm6 or TRPM1. There are five retinal splice variants of TRPM1. Variants containing all six transmembrane domains have a developmental expression profile similar to bipolar cells. Immunohistochemical analysis shows TRPM1 is localized to BC somas and dendritic tips where it co-localizes with YFP-nyctalopin. Nyctalopin interacts with the TRPMl channel is required for proper localization of the TRPMl channel to the bipolar cell dendritic tips.
Pearring, Jillian Nydam, "Nyctalopin is required for localization of the TRPM1 channel to the retinal depolarizing bipolar cell dendrites." (2010). Electronic Theses and Dissertations. Paper 1107.