Lee Harkless
Understanding regulatory influence on differential phototransduction cascades of ipRGC subtypes
The mouse retina contains three photoreceptors: rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). Rods and cones are a uniform cell type with a single, well-defined phototransduction cascade. IpRGCs instead are highly heterogeneous, comprising 6 unique subtypes. IpRGC subtypes vary based on morphology, such as soma size, dendritic field size, and stratification. IpRGCs also vary in their transcriptome and electrophysiological responses to light, which my work focuses on. Two subtypes, the M1 and M4 ipRGCs, appear to utilize different G-protein mediated phototransduction cascades downstream of melanopsin. My work explores how two distinct regulatory mechanisms may influence the G-protein specificity of melanopsin. The differential expression of regulatory proteins across subtypes can serve as a mechanism to achieve a Gq-mediated cascade in M1 ipRGCs, and a non-Gq-mediated cascade in M4 ipRGCs. Because amino acid structure has not yet been observed to fully determine the G-protein signaling profile of a GPCR, my research seeks to identify a novel mechanism of G-protein “switching” through which regulatory proteins define the downstream signaling cascade that melanopsin initiates.