Neuron-Subtype-Specific Expression, Interaction Affinities, and Specificity Determinants of DIP/Dpr Cell Recognition Proteins

Abstract

SUMMARY Binding between DIP and Dpr neuronal-recognition proteins has been proposed to regulate synaptic connections between lamina and medulla neurons in the Drosophila visual system. Each lamina neuron was previously shown to express many Dprs. Here, we demonstrate, by contrast, that their synaptic partners typically express one or two DIPs, with binding specificities matched to the lamina neuron-expressed Dprs. A deeper understanding of the molecular logic of DIP/Dpr interaction requires quantitative studies on the properties of these proteins. We thus generated a quantitative affinity-based DIP/Dpr interactome for all DIP/Dpr protein family members. This revealed a broad range of affinities and identified homophilic binding for some DIPs and some Dprs. These data, along with full-length ectodomain DIP/Dpr and DIP/DIP crystal structures, led to the identification of molecular determinants of DIP/Dpr specificity. This structural knowledge, along with a comprehensive set of quantitative binding affinities, provides new tools for functional studies in vivo.

Interactions with presynaptic photoreceptors mediated by the Dpr11 and DIP-γ cell surface proteins control selection and survival of Drosophila amacrine neurons

“…Thus, Tm5a and Tm5b represent separate output channels for y (Rh4) and p (Rh3) inputs for this set of columns (see Table 1-table supplement legend). Tm5a expresses DIP-γ, while Tm5b does not (Cosmanescu et al, 2018). This suggests that the selective connection of yR7 to both yDm8 and Tm5a in the home column might involve Dpr11-DIP-γ interactions.…”

“…Dprs are 2-IgSF domain CSPs and interact with DIPs, which are 3-IgSF domain CSPs. KDs shown here are from (Cosmanescu et al, 2018). Ig domains indicated by ovals.…”

“…Our analysis of the patterns of synaptic connections defined by the EM reconstruction of the medulla (Takemura et al, 2013;Takemura et al, 2015) indicates that yR7 and yDm8 both preferentially synapse onto Tm5a, while pR7 and pDm8 synapse onto Tm5b (Table 1). Tm5a expresses DIP-γ, while Tm5b does not (Cosmanescu et al, 2018), so Dpr11-DIP-γ interactions might be involved in specifying both yR7-yDm8 and yR7-Tm5a connections. Four of the seven Dm8 neurons, and three of the eight R7 PRs, also make a few synapses onto Tm5c neurons, which are required for innate UV preference (Karuppudurai et al, 2014) (Table 1-table supplement).…”

“…The current Dpr-ome has 21 2-IgSF Dpr proteins (Nakamura et al, 2002), each of which binds to one or more of the 11 3-IgSF DIP proteins. Most DIPs interact with multiple Dprs and vice versa, and their binding affinities vary between 1 and 200 µM (Cosmanescu et al, 2018). Each DIP and Dpr is expressed in a unique subset of neurons at each stage of development.…”

“…Each DIP and Dpr is expressed in a unique subset of neurons at each stage of development. In the visual system, neurons expressing a DIP tend to be postsynaptic to neurons that express a Dpr to which that DIP binds in vitro Cosmanescu et al, 2018;Davis et al, 2018;Tan et al, 2015;Xu et al, 2018b). DIPs and Dprs define an IgSF family, present in both protostomes and deuterostomes, that has been denoted as the Wirins.…”