System and method for controlling G-protein coupled receptor pathways
A light-sensitive G-protein coupled receptor includes a light sensitive extracellular cone opsin or melanopsin domain and a hetorologous intracellular domain capable of modulating an intracellular signaling pathway.
1. A light-sensitive G-protein coupled receptor comprising:
a light sensitive extracellular melanopsin domain, the intracellular domain corresponding to at least a portion of the 5HT receptor domain effective to modulate serotonergic signaling, and a heterologous intracellular domain capable of modulating an intracellular signaling pathway, the melanopsin domain comprising a native vertebrate melanopsin (vMo) amino acid sequence.
2. The light-sensitive G-protein coupled receptor of claim 1 , the melanopsin selected from the group consisting of human melanopsin (huMo) and mouse melanopsin (moMo).
3. The light-sensitive G-protein coupled receptor of claim 2 , the melanopsin comprising a long mouse melanopsin (mOpn4L).
4. The light-sensitive G-protein coupled receptor of claim 1 , the intracellular domain coupling a G-protein subunit to affect at least one G-protein pathway selected from group of Gi, Gq, and Gs.
5. The light-sensitive G-protein coupled receptor of claim 1 , the intracellular domain comprising an amino acid sequence corresponding to an amino acid sequence of at least one 5HT intracellular loop selected from the group consisting of a 5HT-2A loop, a 5HT-1A loop, and a 5HT-4A loop.
6. A light-sensitive G-protein coupled receptor comprising:
a light sensitive extracellular melanopsin domain, the melanopsin domain comprising an amino acid sequence corresponding to a native vertebrate melanopsin (vMo) wherein the melanopsin EF loop amino acid sequence is replaced by a heterologous GPCR EP loop amino acid sequence, and
a heterologous intracellular domain capable of modulating an intracellular signaling pathway the intracellular domain corresponding to at least a portion of the 5HT receptor domain effective to modulate serotonergic signaling.
7. The light-sensitive G-protein coupled receptor of claim 6 , the melanopsin selected from the group consisting of human melanopsin (huMo) and mouse melanopsin (moMo).
8. The light-sensitive G-protein coupled receptor of claim 7 , the melanopsin comprising a long mouse melanopsin (mOpn4L).
9. The light-sensitive G-protein coupled receptor of claim 6 , the intracellular domain coupling a G-protein subunit to affect at least one G-protein pathway selected from group of Gi, Gq, and Gs.
10. The light-sensitive G-protein coupled receptor of claim 6 , the intracellular domain comprising an amino acid sequence corresponding to an amino acid sequence of at least one 5HT intracellular loop selected from the group consisting of a 5HT-2A loop, a 5HT-1A loop, and a 5HT-4A loop.