The NGL family of leucine-rich repeat-containing synaptic adhesion molecules.
Cell adhesion molecules at neuronal synapses regulate diverse aspects of synaptic development, including axo-dendritic contact establishment, early synapse formation, and synaptic maturation. Recent studies have identified several synaptogenic adhesion molecules. The NGL (netrin-G ligand; LRRC4) family of synaptic cell adhesion molecules belongs to the superfamily of leucine-rich repeat (LRR) proteins. The three known members of the NGL family, NGL-1, NGL-2, and NGL-3, are mainly localized to the postsynaptic side of excitatory synapses, and interact with the presynaptic ligands, netrin-G1, netrin-G2, and LAR, respectively. NGLs interact with the abundant postsynaptic density (PSD) protein, PSD-95, and other postsynaptic proteins, including NMDA receptors. These interactions are thought to couple synaptic adhesion events to the assembly of synaptic proteins. In addition, NGL proteins regulate axonal outgrowth and lamina-specific dendritic segmentation, suggesting that the NGL-dependent adhesion system is important for the development of axons, dendrites, and synapses. Consistent with these functions, defects in NGLs and their ligands are associated with impaired learning and memory, hyperactivity, and an abnormal acoustic startle response in transgenic mice, and schizophrenia, bipolar disorder, and Rett syndrome in human patients.
Woo
Jooyeon
J
National Creative Research Initiative Center for Synaptogenesis, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
Kwon
Seok-Kyu
SK
Kim
Eunjoon
E
D000818:Animals; D000090263:Leucine-Rich Repeat Proteins; D008954:Models, Biological; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism; D019006:Neural Cell Adhesion Molecules / Q000737:chemistry / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*
D000090263:Leucine-Rich Repeat Proteins; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D011506:Proteins; C033652:postsynaptic density proteins