Abstract
Nyctalopin is a small leucine rich repeat proteoglycan (SLRP) whose function is critical for normal vision. The absence of nyctalopin results in the complete form of congenital stationary night blindness. Normally, glutamate released by photoreceptors binds to the metabotropic glutamate receptor type 6 (GRM6), which through a G-protein cascade closes the non-specific cation channel, TRPM1, on the dendritic tips of depolarizing bipolar cells (DBCs) in the retina. Nyctalopin has been shown to interact with TRPM1 and expression of TRPM1 on the dendritic tips of the DBCs is dependent on nyctalopin expression. In the current study, we used yeast two hybrid and biochemical approaches to investigate whether murine nyctalopin was membrane bound, and if so by what mechanism, and also whether the functional form was as a homodimer. Our results show that murine nyctalopin is anchored to the plasma membrane by a single transmembrane domain, such that the LRR domain is located in the extracellular space.
Highlights
Nyctalopin is a small leucine rich repeat containing protein that is required for normal vision [1,2] and is localized to the dendritic tips of depolarizing bipolar cells (DBCs) [3]
When there is an increase in light intensity, glutamate release from photoreceptors is decreased, which leads to reduced GRM6 receptor activity, inactivation of the G-protein cascade and opening of the TRPM1 channel, causing depolarization of the DBCs
Previous data showed that mutations in nyctalopin predicted to cause a loss of nyctalopin in humans and mouse, result in the absence of b-wave in the ERG [1,2,6], indicating signaling between the GRM6 receptor and TRPM1 is defective
Summary
Nyctalopin is a small leucine rich repeat containing protein that is required for normal vision [1,2] and is localized to the dendritic tips of depolarizing bipolar cells (DBCs) [3]. At the C-terminus of human nyctalopin there is a consensus sequence for addition of a glycosylphosphatidylinositol (GPI) anchor [1,2]. In mouse this site appears to be absent, rather there may be one or more transmembrane domains [6]. We used a combination of yeast two-hybrid and in-vitro translation approaches to investigate whether murine nyctalopin is oriented with the N-terminus in the extracellular space and if it is anchored to the membrane by a single transmembrane domain. We examined whether nyctalopin could form homo-dimers in yeast
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