Molecular basis of synaptic specificity by immunoglobulin superfamily receptors in Drosophila

eLife

Meike Lobb-Rabe¹  Robert A Carrillo²  Shouqiang Cheng³  Engin Özkan³  Justyna D Kurleto³  James Ashley⁴  Yeonhee Jenny Park⁴ 

[1] Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland;Graduate Program in Cell and Molecular Biology, University of Chicago, Chicago, United States;Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States;Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United States;

关键词: cell surface receptors;    immunoglobulin superfamily;    synapse specificity;    neuromuscular system;    crystal structure;    protein engineering;   

DOI  :  10.7554/eLife.41028

来源: DOAJ

【 摘 要 】

In stereotyped neuronal networks, synaptic connectivity is dictated by cell surface proteins, which assign unique identities to neurons, and physically mediate axon guidance and synapse targeting. We recently identified two groups of immunoglobulin superfamily proteins in Drosophila, Dprs and DIPs, as strong candidates for synapse targeting functions. Here, we uncover the molecular basis of specificity in Dpr–DIP mediated cellular adhesions and neuronal connectivity. First, we present five crystal structures of Dpr–DIP and DIP–DIP complexes, highlighting the evolutionary and structural origins of diversification in Dpr and DIP proteins and their interactions. We further show that structures can be used to rationally engineer receptors with novel specificities or modified affinities, which can be used to study specific circuits that require Dpr–DIP interactions to help establish connectivity. We investigate one pair, engineered Dpr10 and DIP-α, for function in the neuromuscular circuit in flies, and reveal roles for homophilic and heterophilic binding in wiring.

【 授权许可】

Unknown