Semaphorin 4F (Sema4F; previously called Sema W) is a 100-150kD member of the class 4 family of type I transmembrane semaphorins (1-3). Mature mouse Sema4F is a 737 amino acid (aa) protein that contains a Sema domain, a PSI region, and a C2-type Ig-like domain within its extracellular domain (ECD; aa41-667) (2). Within the ECD, mouse Sema4F shares 92% and 98% aa identity with human and rat Sema4F, respectively. Sema4F is expressed by cell types that include Schwann cells, oligodendrocyte (highest in precursors), retinal ganglion cells, and neurons, especially along migratory pathways (2-4). It is found within post-synaptic densities at glutamatergic synapses, where it binds and probably recruits the cytoplasmic scaffolding protein PSD-95 (3, 5). In Schwann cells, Sema4F likely acts as an adhesive protein and a mediator of contact inhibition, and thus an inhibitor of cell proliferation (6). In neurofibromatosis type 1 (NT1), loss of the NF1 protein results in loss of Schwann cell Sema4F expression via perturbation of ERK signals (6). Loss of Sema4F in turn disrupts adhesive interaction and alignment of Schwann cells with neurons (6). For oligodendroglial precursors in culture, immobilized Sema4F inhibits migration and enhances survival, differentiation and adhesion (3). A secreted form of ~80kD is reported in prostate cancer cells, transfected cell culture supernatants, and adult brain lysates (3, 7).
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