Editors' ChoiceCell Biology

Toxin Receptors Unite

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Science Signaling  27 Mar 2012:
Vol. 5, Issue 217, pp. ec94
DOI: 10.1126/scisignal.2003073

Neurexins (neurexin 1, 2, and 3, each of which have short and long forms and multiple splice variants) are a family of neuronal proteins with a single membrane-spanning domain, and CL proteins (CL1, CL2, and CL3) are members of the cell adhesion class of G protein–coupled receptors. CL1, CL3, and neurexins are present in neurons. CLs and neurexins lacking the SS4 spliced insert bind to the black widow toxin α-latrotoxin, and neurexins have been implicated in various neurological disorders. Noting that both classes of proteins could bind the spider toxin, Boucard et al. investigated whether the extracellular domains of these two families of proteins interacted using various qualitative and quantitative surface binding assays with transfected cells and labeled proteins. These assays indicated that neurexins lacking the SS4 insert bound to CL1 with nanomolar affinity. Cell aggregation was observed when human embryonic kidney 293 cells independently transfected with either neurexin lacking SS4 insert or with CL1 were mixed. Using the cell-based interaction assay, the interaction between neurexins and CL1 was mapped to the olfactomedin-like domain of CL1. The neurexin domain responsible was assumed to be the LNS (laminin-neurexin-steroid-binding hormone) domain because this is the only extracellular domain present in the short form of neurexins. Whereas neurexins were active in promoting the formation of artificial synapses in transfected nonneuronal cells, transfected CL1 was not functional in this assay. However, CL1 competed for the neurexin ligand neuroligin-1 in the quantitative surface binding assay. Whether these interactions occur in vivo and their functional relevance remain outstanding questions.

A. A. Boucard, J. Ko, T. C. Südhof, High affinity neurexin binding to cell adhesion G-protein-coupled receptor CIRL1/latrophilin-1 produces an intercellular adhesion complex. J. Biol. Chem. 287, 9399–9413 (2012). [Abstract] [Full Text]

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