SEMAs
Definition: Semaphorins are a large family of secreted or cell-bound signals, known to guide axons in developing nervous tissue. Semaphorins are secreted or transmembrane proteins that regulate cell motility and attachment in axon guidance, vascular growth, immune cell regulation and tumour progression.
Semaphorins (SEMAs) compete with vascular endothelial growth factor (VEGF) for receptor neuropilin-1 (NP1) and neuropilin-2 (NP2) and suppress angiogenesis.
The main receptors for semaphorins are plexins (PLXNs), which have established roles in regulating Rho-family GTPases. Plexins can also influence R-Ras, which, in turn, can regulate integrins (ITGs).
Members
| SEMA1 | SEMA2 | |||||
| SEMA3s | SEMA3A | SEMA3B | SEMA3C | SEMA3D | SEMA3E | SEMA3F |
| SEMA4s | SEMA4A | SEMA4B | SEMA4C | SEMA4D | SEMA4E | SEMA4F |
| SEMA5 | SEMA6 | SEMA7 | SEMA8 |
Functions
SEMAs are expressed in a variety of adult and embryonic tissues and are thought to have a broader spectrum of functions. Semaphorins and their receptors play a key role in the control of cellular interactions, most likely in cell-cell repulsion (molecular repellant).
Axon guidance
A subset of semaphorins interacts with neuropilins (NRPS), that are cell-surface molecules lacking a signalling-competent cytoplasmic domain.
Another large family of transmembrane molecules, namely plexins (PLXNs), bind specifically to semaphorins (SEMAs). Thus plexins, alone, or in association with neuropilins (NRPs), behave as fully functional semaphorin receptors.
The main receptors for semaphorins are plexins, which have established roles in regulating Rho-family GTPases. Plexins can influence R-Ras, which, in turn, can regulate integrins.
Angiogenesis
The SEMAs were initially identified through their role in axon guidance. It has recently been reported that SEMAs inhibit the angiogenic effect of VEGF by competition for NRP1 binding.
Pathology
Lung and breast carcinomas were reported to have frequent allelic loss or loss of heterozygosity (LOH) at 3p21.3, where SEMA3B and SEMA3F are located. Thus, SEMA3B and SEMA3F are candidates for tumor suppressor genes.
A balance between SEMA3A and VEGF was reported to induce tumor progression in breast cancer.
References
Osada R, Horiuchi A, Kikuchi N, Ohira S, Ota M, Katsuyama Y, Konishi I. Expression of semaphorins, vascular endothelial growth factor, and their common receptor neuropilins and alleic loss of semaphorin locus in epithelial ovarian neoplasms: increased ratio of vascular endothelial growth factor to semaphorin is a poor prognostic factor in ovarian carcinomas. Hum Pathol. 2006 Nov;37(11):1414-25. PMID: #17010410#
Kruger RP, Aurandt J, Guan KL. Semaphorins command cells to move. Nat Rev Mol Cell Biol. 2005 Oct;6(10):789-800. PMID: #16314868#
Tamagnone L, Comoglio PM. Signalling by semaphorin receptors: cell guidance and beyond.Trends Cell Biol. 2000 Sep;10(9):377-83. PMID: #10932095#