This entry represents the sema domain of Semaphorin-3A []. Sema3A has been reported to inhibit the growth of certain experimental tumours and to regulate endothelial cell migration and apoptosis in vitro, as well as arteriogenesis in the muscle, skin vessel permeability, and tumor angiogenesis in vivo []. The function of Sema3A is mediated through receptors neuropilin-1 (NP1) and plexins, although little is known about the requirement of specific plexins in its receptor complex []. It is known however that Plexin-A4 is the receptor for Sema3A in the Toll-like receptor- and sepsis-induced cytokine storm during immune response []. Sema3A is a member of the Class 3 semaphorin family of secreted proteins []. Semaphorins are regulatory molecules in the development of the nervous system and in axonal guidance. They also play important roles in other biological processes, such as angiogenesis, immune regulation, respiration systems and cancer. The Sema domain is located at the N terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a receptor-recognition and -binding module [].
Plexin A1 is found in both the nervous and immune systems. Its external Sema domain is also shared by semaphorin proteins. In the nervous system, Plexin A1 mediates Sema3A axon guidance function by interacting with the Sema3A coreceptor neuropilin, resulting in actin depolarization and cell repulsion [, ]. In the immune system, Plexin A1 mediates Sema6D signaling by binding to the Sema6D-Trem2-DAP12 complex on immune cells and osteoclasts to promote Rac activation and DAP12 phosphorylation []. In gene profiling experiments, Plexin A1 was identified as a CIITA (class II transactivator) regulated gene in primary dendritic cells (DCs) []. The Sema domain is located at the N terminus and contains four disulfide bonds formed by eight conserved cysteine residues. It serves as a ligand-recognition and -binding module.
Semaphorins were first cloned as recognised mediators of cellular guidance, and consist of a large family of phylogenetically conserved secreted and transmembrane signalling proteins. Among the best-characterised vertebrate Semaphorins are the five secreted Class 3 members that contain an approximately 500 amino acid N-terminal Semaphorin domain, a C2 type immunoglobulin domain, and a highly basic C-terminal tail []. Two receptor families have been implicated in mediating the actions of class 3 semaphorins: the Neuropilins and Plexins. The nine known vertebrate Plexins are divided into four subfamilies (A through D) based on structure []. Several Plexins have been shown to interact directly with some class 4, 7 and V Semaphorins, but class 3 Semaphorins, however, do not appear to bind Plexins directly. Rather, the functional receptors for these Semaphorins are complexes of Neuropilins and A-type Plexins, with the former serving as the ligand-binding moiety and the latter the signal-transducing component [, ]. There are two Neuropilins (NP-1 and NP-2) that bind the five class 3 Semaphorins preferentially. In particular, Sema3A binds NP-1, whereas Sema3F utilises NP-2, while NP-1 and NP-2 heterodimers are thought to serve as functional receptors for Sema3C [].Semaphorin 4F may be involved in the injury response of intramedullary axotomized motoneurons [].
Semaphorins were first cloned as recognised mediators of cellular guidance, and consist of a large family of phylogenetically conserved secreted and transmembrane signalling proteins. Among the best-characterised vertebrate Semaphorins are the five secreted Class 3 members that contain an approximately 500 amino acid N-terminal Semaphorin domain, a C2 type immunoglobulin domain, and a highly basic C-terminal tail []. Two receptor families have been implicated in mediating the actions of class 3 semaphorins: the Neuropilins and Plexins. The nine known vertebrate Plexins are divided into four subfamilies (A through D) based on structure []. Several Plexins have been shown to interact directly with some class 4, 7 and V Semaphorins, but class 3 Semaphorins, however, do not appear to bind Plexins directly. Rather, the functional receptors for these Semaphorins are complexes of Neuropilins and A-type Plexins, with the former serving as the ligand-binding moiety and the latter the signal-transducing component [, ]. There are two Neuropilins (NP-1 and NP-2), which bind the five class 3 Semaphorins preferentially. In particular, Sema3A binds NP-1, whereas Sema3F utilises NP-2, while NP-1 and NP-2 heterodimers are thought to serve as functional receptors for Sema3C [].Recent work suggests a possible role of Gallus gallus (Chicken) Sema3E/collapsin-5 in restricting growth of retinal ganglion cell axons to the optic fibre layer [].
Semaphorins were first cloned as recognised mediators of cellular guidance, and consist of a large family of phylogenetically conserved secreted and transmembrane signalling proteins. Among the best-characterised vertebrate Semaphorins are the five secreted Class 3 members that contain an approximately 500 amino acid N-terminal Semaphorin domain, a C2 type immunoglobulin domain, and a highly basic C-terminal tail []. Two receptor families have been implicated in mediating the actions of class 3 semaphorins: the Neuropilins and Plexins. The nine known vertebrate Plexins are divided into four subfamilies (A through D) based on structure []. Several Plexins have been shown to interact directly with some class 4, 7 and V Semaphorins, but class 3 Semaphorins, however, do not appear to bind Plexins directly. Rather, the functional receptors for these Semaphorins are complexes of Neuropilins and A-type Plexins, with the former serving as the ligand-binding moiety and the latter the signal-transducing component [, ]. There are two Neuropilins (NP-1 and NP-2) that bind the five class 3 Semaphorins preferentially. In particular, Sema3A binds NP-1, whereas Sema3F utilises NP-2, while NP-1 and NP-2 heterodimers are thought to serve as functional receptors for Sema3C [].Recent microarray studies have suggested a role for Sema 6C in dental mesenchyme-induced neurite repulsion [].
