A team led by Yoshikazu Imanishi, assistant professor of pharmacology, recently conducted research on the behavior of a ciliary G protein coupled receptor (GPCR), Rhodopsin, by using genetically engineered tadpoles.
The team’s paper “Signals Governing the Trafficking and Mistrafficking of a Ciliary GPCR, Rhodopsin” was published in the Journal of Neuroscience on Aug. 21. Other team members were Kerrie H. Lodowski, Richard Lee, Philip Ropelewski, Ina Nemet and Guilian Tian.
When the normal trafficking of rhodopsin in the eye is disrupted, humans can become blind. An amino acid signaling motif, QVAPA, is believed to be essential for rhodospin trafficking. This sequence is lost in some individuals with a naturally occurring genetic mutation. The molecular mechanisms for how this mistrafficking occurs however, remains unclear. Why does rhodopsin behave so detrimentally when this sequence becomes lost?
To investigate this question, the researchers used tadpoles genetically engineered to express rhodopsin fusion proteins in the rod cells of their eyes.
In their study, the researchers found a novel mislocalization signal that leads to rhodopsin mistrafficking in the absence of the QVAPA sequence. When this signal is removed from the QVAPA deficient protein, protein localization becomes similar to wild-type rhodopsin. Additionally, the photoreceptor toxicity that is observed in these QVAPA deficient tadpoles is ameliorated.
