Semaphorin 3A [Sema-3A]

Semaphorin-3A is encoded by the SEMA3A (COLL1) gene (gene ID: 395825) in chicken. Semaphorin-3A is a secreted protein that is synthesized with a 22 amino acid signal peptide. It is a member of a family of proteins that are involved in cell migration and axonal growth cone guidance. Semaphorin-3A has an Ig-like C2-type (immunoglobulin-like) domain, a PSI domain, and a Sema domain of 500 amino acids. It strongly binds to neuropilin via its carboxy third sequence and competes with semaphorin dimerization. It is expressed at relatively high levels in brain and muscle and at moderate levels in lung, bursa, and heart. It is not found in the liver. Semaphorin-3A can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical dendrites. It induces the collapse and paralysis of neuronal growth cones and could serve as a ligand that guides specific growth cones by a motility-inhibiting mechanism. Increased expression of Semaphorin-3A is associated with schizophrenia, and it is seen in a variety of human tumor cell lines. Additionally, aberrant release of this protein is associated with the progression of Alzheimer’s disease. Semaphorin-3A is also reported to exert an osteoprotective effect by both suppressing osteoclastic bone resorption and increasing osteoblastic bone formation. The downregulation of Semaphorin-3A expression is shown to cause ischemia, degenerative diseases, and multiple sclerosis.