juxtacrine

Juxtacrine signaling is a mode of cell-to-cell communication that requires direct contact between neighboring cells. In this form of signaling, the signaling molecule is typically a membrane-bound ligand presented on the surface of the signaling cell, while the corresponding receptor is on the adjacent responding cell. Because the ligand is not released into the extracellular space, juxtacrine signaling exerts its effects only on immediately neighboring cells, in contrast to paracrine or endocrine signaling that rely on diffusible factors.

Several well-studied juxtacrine pathways illustrate the range of mechanisms involved. Notch signaling is a classic example, where membrane-tethered ligands such as Delta-like or Jagged proteins on one cell engage the Notch receptor on a neighboring cell, triggering proteolytic cleavages that release an intracellular domain that modulates gene expression. Another notable pathway involves ephrin ligands and Eph receptors, where cell–cell contact influences cell adhesion, migration, and boundary formation. In addition, gap junctions provide a form of juxtacrine communication by allowing direct cytoplasmic exchange of ions and small metabolites between adjacent cells, effectively coordinating cellular states.

Biological roles of juxtacrine signaling include tissue development and patterning, maintenance of cell identity, immune cell interactions, and vascular or organogenesis processes. Dysregulation of juxtacrine signals, particularly Notch signaling, is implicated in developmental disorders and various diseases, including cancer. The concept emphasizes how cells can convey information and regulate each other through immediate, contact-dependent mechanisms.