NetrinGLiganden

Netrin-G ligands, or Netrin-G1 and Netrin-G2, are a small family of vertebrate proteins that function as axonal guidance cues and synaptic adhesion molecules. They are GPI-anchored, extracellular proteins expressed on presynaptic membranes and act as ligands for postsynaptic receptors in the NGL family. The NTNG1 and NTNG2 genes encode these ligands in humans and other jawed vertebrates.

In the synapse, Netrin-G ligands form a trans-synaptic adhesion complex with their corresponding NGL receptors on the postsynaptic side. This interaction contributes to the specificity and maturation of synapses, helping align presynaptic and postsynaptic elements and influence the formation of functional neural circuits. The activity of Netrin-G ligands has been particularly associated with excitatory synapses in cortical and hippocampal networks, where precise connectivity patterns are essential for higher-order processing.

Expression of Netrin-G ligands is developmentally regulated and shows region-specific patterns in the brain. Netrin-G1 and Netrin-G2 can exhibit complementary or overlapping distributions, supporting distinct circuit assembly programs as the nervous system matures. Their accessibility and extracellular nature have also made them a subject of study for understanding synaptic organization and plasticity.

Genetic and association studies have explored links between NTNG genes and neuropsychiatric conditions, including schizophrenia and autism spectrum disorders, though findings vary and causal relationships remain to be established. Overall, Netrin-G ligands are recognized as important contributors to synaptic connectivity and neural circuit formation in the vertebrate brain.