SEMA3As

SEMA3A, or semaphorin-3A, is a secreted member of the class 3 semaphorins that functions as a guidance cue during development and in various physiological processes. It is encoded by the SEMA3A gene and is produced as a soluble protein that can influence the movement and behavior of neighboring cells.

SEMA3A signals through receptor complexes that typically include neuropilin-1 (NRP1) and one or more plexins, especially PLXNA1, with other plexins (PLXNA2-4) capable of involvement in certain contexts. Binding of SEMA3A to these receptors activates intracellular signaling cascades that regulate the cytoskeleton, leading to growth cone collapse and repulsive guidance in developing neurons. This signaling also impacts dendritic morphology and the migration of various cell types, including interneurons in the brain.

Beyond the nervous system, SEMA3A influences non-neural tissues by modulating angiogenesis and immune cell behavior. It can exert anti-angiogenic effects by repelling endothelial cells and altering vascular patterning. In the immune system, SEMA3A can affect leukocyte migration and activation, contributing to immune regulation. The role of SEMA3A in cancer is context-dependent, with evidence for both tumor-suppressive and tumor-promoting effects depending on receptor expression and tissue environment.

Expression of SEMA3A is tightly regulated during development and in adulthood. Disturbances in SEMA3A signaling have been linked to neurodevelopmental abnormalities in experimental models, and ongoing research investigates its potential in nerve regeneration, immune modulation, and cancer therapy.