Host: Steve Wilson

Cell surface and secreted proteins are centrally involved in initiating intercellular communication and are encoded by around a fifth of our genes. Despite their importance and abundance, many extracellular proteins have no known binding partners because they are biochemically difficult to manipulate; these proteins are therefore largely absent from recent large-scale interactome datasets.

To address this problem, we have developed an in vitro binding assay called AVEXIS (for AVidity-based EXtracellular Interaction Screen), which circumvents the main biochemical difficulties associated with the identification of extracellular interactions. Using this assay and a library of over 250 zebrafish ectodomain fragments – mainly from the immunoglobulin and leucine-rich-repeat superfamilies – we have identified over 100 novel receptor:ligand pairs.

Wholemount in situ expression patterns of genes encoding interacting proteins revealed that most are expressed in a restricted tissue-specific manner. In addition, interacting pairs are usually expressed in overlapping or adjacent tissues, immediately suggesting potential biological roles.

The in vivo function of selected interactions is being determined by performing loss-of-function experiments on both genes encoding a pair of interacting proteins. Using this approach, we aim to identify novel signalling pathways important for early vertebrate development.

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