Functional significance of a novel guidance receptor in axons and dendrites
Final Report Abstract
During development, neurons send their axons to their correct targets to form a functional circuit. To reveal the key mechanism that regulates the axon pathfinding, a novel axon guidance receptor, Golden goal (Gogo) was identified in the photoreceptor (R) axon in Drosophila. We have proposed that Gogo functions as a receptor that helps photoreceptor axons to recognize their synaptic target layer. To reveal the molecular mechanism that underlies Gogo mediated axon targeting, we have identified that atypical Cadherin Flamingo binds to Gogo in cis to recognize Flamingo on the target side to form homophilic interaction. This combinatorial system serves as the molecular code that encodes wiring specificity, and acts as a key-and-the-lock system between innervating photoreceptor axons and the targeted brain neurons. We found Gogo binds to Acto-Spectrin network in the cytoplasmic domains and may regulate the Actin cytoskeleton directly, and is regulated by the phosphorylation of a conserved motif in the cytoplasmic domain by Insulin receptor. Together with these findings, we have revealed the molecular machinery of Gogo signaling.
Publications
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(2011). Golden Goal Collaborates with Flamingo in Conferring Synaptic-Layer Specificity in the Visual System. Nature Neuroscience 3:314-24
Hakeda-Suzuki S, Berger-Mueller S, Usui T, Horiuchi S, Uemura T, Suzuki T
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(2011). Hts, the Drosophila homologue of Adducin, physically interacts with the transmembrane receptor Golden goal to guide photoreceptor axons. Developmental Dynamics 240: 135-148
Ohler S, Hakeda-Suzuki S, Suzuki T
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(2011). Seven-pass transmembrane cadherins: roles and emerging mechanisms in axonal and dendritic patterning. Mol Neurobiol 44:313-20
Berger-Müller S, Suzuki T
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(2012). A putative tyrosine phosphorylation site of the cell surface receptor Golden goal is involved in synaptic layer selection in the visual system. Development Feb;139(4):760-71
Mann K, Wang M, Luu S-H, Ohler S, Hakeda-Suzuki S, Suzuki T
