The integrity of the glycine co-agonist binding site of N-methyl-D-aspartate receptors is a functional quality control checkpoint for cell surface delivery.

N-Methyl-D-aspartate receptors are a subclass of ligand-gated, heteromeric glutamatergic neurotransmitter receptors whose cell surface expression is regulated by quality control mechanisms. Functional quality control checkpoints are known to contribute to cell surface trafficking of non-N-methyl-D-aspartate glutamate receptors. Here we investigated if similar mechanisms operate for the surface delivery of NMDA receptors.

Assembly and forward trafficking of NMDA receptors (Review).

N-Methyl-D-aspartate (NMDA) receptors are a subclass of the excitatory, ionotropic L-glutamate neurotransmitter receptors. They are important for normal brain function being both primary candidates for the molecular basis of learning and memory and in the establishment of synaptic connections during the development of the central nervous system. NMDA receptors are also implicated in neurological and psychiatric disorders.

Ligand concentration is a driver of divergent signaling and pleiotropic cellular responses to FGF.

Fibroblast growth factors (FGFs) are soluble ligands important for embryonic patterning, limb and brain development, and stem cell proliferation. They activate specific receptors (FGFR) to elicit changes in gene expression and cellular responses such as proliferation, differentiation, and survival, but the extent to which these pleiotropic responses are driven by FGF concentration gradients has not been systematically addressed. Here, we show that a single cell type exhibits divergent, even opposing, responses to a single FGF dependent on the exposure concentration, and that this is controlled by differential signaling with specific negative feedback inhibition.

A peptide from the first fibronectin domain of NCAM acts as an inverse agonist and stimulates FGF receptor activation, neurite outgrowth and survival.

Neural cell adhesion molecule (NCAM) contributes to axon growth and guidance during development and learning and memory in adulthood. Although the Ig domains mediate homophilic binding, outgrowth activity localizes to two membrane proximal fibronectin-like domains. The first of these contains a site identified as a potential FGF receptor (FGFR) activation motif (FRM) important for NCAM stimulation of neurite outgrowth, but its activity has hitherto remained hypothetical.