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Transmitting signals across the synapse Glutamate receptors located on neuronal cells play a role in mediating electrical signals at excitatory synapses. These glutamatergic synapses are extremely important for nearly all cognitive functions. Elegheert et al. analyzed a complex that bridges the synapse, comprising β-neurexin 1, a cell adhesion molecule on the surface of presynaptic axons; cerebellin 1, a synaptic organizer; and the postsynaptic glutamate receptor GluD2. The structural and functional analysis provides insight into the mechanism of synaptic signaling. Science , this issue p. 295

RGM Proteins Members of the repulsive guidance molecule (RGM) family of proteins can be secreted or reside on the surface of cells where they bind to the cell surface receptor, neogenin. The RGM proteins are named for their role in axon guidance for developing neurons, but their function is also linked to a range of human diseases, including inflammation, multiple sclerosis, and cancer. Bell et al. (p. 77 ) solved the crystal structures of the external portions of the RGMB protein with portions of neogenin. The structures revealed interactions of dimers of RGMB with neogenin in which ligand binding induced conformational changes that may initiate intracellular signaling from the receptor. RGM proteins contain a site of autocatalytic cleavage that affects secretion of the proteins, and some disease-associated mutations in RGM proteins were clustered at this site.

Heparan and chondroitin sulfate proteoglycans (HSPGs and CSPGs, respectively) regulate numerous cell surface signaling events, with typically opposite effects on cell function. CSPGs inhibit nerve regeneration through receptor protein tyrosine phosphatase sigma (RPTPs). Here we report that RPTPs acts bimodally in sensory neuron extension, mediating CSPG inhibition and HSPG growth promotion. Crystallographic analyses of a shared HSPG-CSPG binding site reveal a conformational plasticity that can accommodate diverse glycosaminoglycans with comparable affinities. Heparan sulfate and analogs induced RPTPs ectodomain oligomerization in solution, which was inhibited by chondroitin sulfate. RPTPs and HSPGs colocalize in puncta on sensory neurons in culture, whereas CSPGs occupy the extracellular matrix. These results lead to a model where proteoglycans can exert opposing effects on neuronal extension by competing to control the oligomerization of a common receptor.