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Mann, Klaudiusz (2012): Phosphorylation of the cell surface receptor golden goal and layer-specific targeting in drosophila. Dissertation, LMU München: Faculty of Biology
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Abstract

Golden goal (Gogo) is a cell-surface protein critical for proper synaptic layer targeting of photoreceptors in the Drosophila melanogaster visual system. In collaboration with the seven-transmembrane cadherin Flamingo (Fmi), Gogo mediates both temporal and final layer targeting of R cell axons and its cytoplasmic domain is required. However, it is not known how Gogo activity is regulated. I show in my Dissertation that a conserved tripeptide Tyr-Tyr-Asp (YYD motif) in Gogo cytoplasmic domain is required for photoreceptor axon targeting. Deleting the YYD motif is sufficient to completely abolish Gogo function. I demonstrate that the YYD motif is a phosphorylation site and that mutations in the YYD tripeptide impair synaptic layer targeting. Gogo phosphorylation results in premature axon stopping and dephosphorylation is crucial for the collaboration with Fmi during the final target layer targeting. Therefore, both temporal and final layer targeting strongly depend on Gogo phosphorylation status. Drosophila Insulin Receptor (DInR) has been reported to regulate wiring of photoreceptors in the fly. I show that insulin signaling is a positive regulator of YYD motif phosphorylation in a direct or indirect way. My findings suggest a novel mechanism of the regulation of Gogo activity by phosphorylation which can be induced by insulin signaling. I propose the model that a constant phosphorylation signal is antagonized by a presumably temporal dephosphorylation signal, which creates a permissive signal that could govern developmental timing in axon targeting.