Semaphorins receptors

Aurandt, J., Vikis, H. G., Gutkind, J. S., Ahn, N., and Guan, K. L. (2002). The semaphorin receptor plexin-Bl signals through a direct interaction with the Rho-specific nucleotide exchange factor, LARG. Proc. Natl. Acad. Sci. USA 99, 12085-12090. 

Fig. 9. Non-covalent semaphorin dimerization mediated by the sema domains. (A) The Sema3A-65K dimer in the asymmetric unit of the crystals. (B) The interacting sema domains in the Sema4D dimer viewed in the same orientation as in (A). The expansive dimerization interface (total buried area of approximately 3000 A ) is generated by the approximation of four protruding loops from each monomer. These loops, located at the top face of the fi propeller are also implicated in interactions with the semaphorin receptors.

Plexins comprise a family of transmembrane proteins that serve as receptors for semaphorins. On the basis... 

The Sema domain consisting of about 500 amino acids is characterized by highly conserved cysteine residues that form intramolecular disulfide bonds. Crystal structures have revealed that the Sema domain folds in the manner of the (3 propeller topology which is also found in integrins or the low-density lipoprotein (LDL) receptors. Sema domains are found in semaphorins, plexins and in the receptor tyrosine kinases Met and Ron. 

Semaphorins are secreted, membrane-associated or transmembrane proteins defined by the presence of a sema-phorin protein domain (Serna domain). In the mammalian system, more than 20 semaphorins have been identified which play important roles in a variety of tissues. The best characterized receptors for mediating semaphoiin effects are members of the neuropilin and plexin families of transmembrane proteins. Semaphoiin functions are best described in the regulation of neural development, angiogenesis, immunoregulation and cancer. 

Neuropilin-1 (NRP1), a molecule that had been previously shown to be implicated in axon guidance as a receptor for members of collapsin/semaphorin family, has been characterized as a which interacts with the heparin-binding VEGF isoforms. 

Fig. 7. Schematic representation of the domain organizadon, as well as ligand-, receptor-, and co-receptor-binding preferences of the semaphorins and their neuronal receptors. The individual domains are labeled. PSI, Plexin/Semaphorin//ntegrin domain IPX, /mmunoglobulin-like domain found in Plexins (and Met) and in some Transcription factors CUB, domain homologous to complement-binding factors Clr and Cls FV/VIII, domain homologous to coagulation factor V and VIII (also known as F5/8 type C or discoidin domain) MAM, Meprin/A5/fi domain SP, Sex-Plexin domain. Semaphorins, plexins and scatter-factor receptors (MET) share a common semaphorin domain (black heptagon).

Vertebrate A-Plexins are the signaling subunits for secreted class 3 semaphorins, while other plexins interact with semaphorins from different classes (Fiore and Piischel, 2003). In contrast to SemaSA, which is not able to bind directly to A-Plexins, SemalD and Sema7A directly interact with Plexin-Bl and Plexin-Cl, respectively (Takahashi et al, 1999 Tamagnone et al, 1999). Interestingly, all Plexins contain an extracellular semaphorin domain that is strictly required for their function (Fig. 7). A semaphorin domain is also present in the scatter-factor receptor MET (Tamagnone et al, 1999). 

He, Z., and Tessier-Lavigne, M. (1997). Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. CeU90, 739-751. 

Renzi, M. J., Feiner, L., Koppel, A. M., and Raper, J. A. (1999). A dominant negative receptor for specific secreted semaphorins is generated by deleting an extracellular domain from neuropiIin-1./. Neurosci. 19, 7870-7880. 

Takahashi, T., Fournier, A., Nakamura, F., Wang, L. H., Murakami, Y., Kalb, R. G., Fujisawa, H., and Strittmatter, S. M. (1999). Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors. Cell 99, 59-69. 

---