The Semaphorins make up the largest family of axon guidance cues yet described. Semaphorins are divided into 8 classes (classes 3-7 found in vertebrates). Class 3 Semaphorins are secreted, classes 4 through 6 are transmembrane proteins, and class 7 are membrane associated via glycosylphosphatidylinositol (GPI) linkage. They are characterized structurally by a conserved ~400 amino acid sema domain. They are classically described as collapsing factors and mediators of axon repulsion, although they may also act as context-dependent chemoattractants. Semaphorins have been shown to have roles in cardiovascular development and in the regulation of immune cell antigen presentation. Receptors or receptor complexes that mediate semaphorin signaling include proteins of the Neuropilin and Plexin families.
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