Netrin-G ligand-3 (NGL-3) (NGL-3)

Netrin-G ligand-3 (NGL-3), encoded by the LRRC4B gene, is a postsynaptic cell adhesion molecule belonging to the leucine-rich repeat (LRR) family (Woo et al., 2009). It plays a critical role in the development and maintenance of excitatory synapses in the central nervous system (J Biol Chem, 2010). Unlike other NGL family members that bind to netrin-Gs, NGL-3 interacts trans-synaptically with the leukocyte antigen-related (LAR) family of receptor protein tyrosine phosphatases, including LAR, PTPδ, and PTPσ (Woo et al., 2009; J Biol Chem, 2010). This interaction facilitates bidirectional signaling that promotes both pre- and postsynaptic differentiation, recruiting scaffolding proteins such as PSD-95 (Mol Cell Neurosci, 2009). Genetic variations and expression changes in NGL-3 and its binding partners have been implicated in various neurodevelopmental and psychiatric disorders, such as autism spectrum disorder, schizophrenia, and ADHD (Frontiers, 2019; PMC, 2019). In oncology, NGL-3 and related family members like LRRC4 are studied for their potential roles as tumor suppressors or markers of disease progression (Mol Cancer, 2014). While NGL-3 is a promising target for modulating synaptic connectivity and neural repair, there are currently no approved drugs targeting this molecule.

Other names

LRRC4BLeucine-rich repeat-containing protein 4BNGL3Netrin-G1-like protein

Modulation of synaptic connectivity through trans-synaptic interaction with leukocyte antigen-related (LAR) family receptor tyrosine phosphatases, inducing bidirectional pre- and postsynaptic differentiation (J Biol Chem, 2010; PMC 6550371).