Drosophila Dprs (defective proboscis-extension response) and DIPs (Dpr-interacting proteins) are two families of immunoglobulin-like cell-recognition proteins, with 11 DIP subtypes and 21 Dpr subtypes expressed in the developing fly brain.  We have experimentally measured the protein-protein interactions between all DIPs and Dprs, revealing a complex interactome. Selectivity subgroups, with members sharing overlapping binding preferences, reflect DIP and Dpr phylogeny. Interactions of a given DIP mainly fall within a single Dpr subgroup, and vice versa, with sparse and weak interactions to members of other subgroups. Crystal structures reveal the molecular details of DIP/Dpr and DIP/DIP interactions, and site-directed mutants enabled the design of site-directed mutants to impact these interactions.  Finally, from neuronal guidance phenotypes in vivo with recombinant flies encoding mutant DIPs and Dprs, we tease out the role of these two protein families in neuronal patterning.

Patterning the nervous system with DIPs and Dprs

ACS Spring 2022

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