Neogenin 1 (NEO1)

Neogenin 1 (NEO1) is a multi-domain transmembrane cell surface receptor in the immunoglobulin superfamily, closely related to the tumor suppressor DCC. Neogenin 1 binds various ligands, including netrin-1, netrin-4, and repulsive guidance molecules (RGMs), and regulates key developmental processes such as axonal guidance, angiogenesis, neural migration, and cell adhesion. In embryogenesis, neogenin 1 controls cell trafficking and survival, operating as a dependence receptor: it promotes apoptosis when unbound by ligand and supports cell survival or migration when occupied by netrin or RGM. In the adult, NEO1 maintains blood-brain barrier integrity and homeostasis, particularly via astrocytic signaling in the brain. Pathologically, abnormal expression of Neogenin 1 is implicated in several cancers, notably neuroblastoma, where high NEO1 and netrin-4 levels predict poor patient prognosis and drive tumor cell migration and metastasis. No targeted therapeutics for NEO1 are currently approved or in clinical use. Elevated NEO1 may serve as a biomarker for aggressive tumor behavior and poor survival. Manipulation of neogenin 1 signaling carries risks due to its diverse roles in vital developmental and homeostatic pathways.

Other names

NeogeninNEO1IGDCC2NGNHsT17534NTN1R2immunoglobulin superfamily DCC subclass member 2neogenin homolog 1

Ligand binding (e.g., netrin-1, netrin-4, RGM family) to Neogenin 1 regulates cell migration, survival, and axonal guidance, switching between pro-apoptotic and pro-survival signaling depending on ligand presence. Netrin-neogenin interaction induces a chemotactic axon guidance response and cell-cell adhesion. Acts as a dependence receptor: promotes survival with ligand, apoptosis without ligand.