Advances in the Cellular and Molecular Biology of Angiogenesis 1565 Class 3 semaphorins and their receptors in physiological and pathological angiogenesis

Class 3 semaphorins (Sema3) are a family of secreted proteins that were originally identified as axon guidance factors mediating their signal transduction by forming complexes with neuropilins and plexins. However, the wide expression pattern of Sema3 suggested additional functions other than those associated with the nervous system, and indeed many studies have now indicated that Sema3 proteins and their receptors play a role in angiogenesis. The present review specifically focuses on recent evidence for this role in both physiological and pathological angiogenesis. Structure and binding specificity of class 3 semaphorins (Sema3) There are eight different classes of semaphorins, of which five classes are found in vertebrates (reviewed in [1]). Sema3 consist of seven secreted glycoproteins of ∼100 kDa containing a conserved 500-amino-acid N-terminal region organized into a seven-blade β-propeller structure called the sema domain, an Ig-like domain and a basic C-termina