The plexin family includes receptors for semaphorin ligands (82, 83). Most semaphorins bind directly to plexin receptors, but class 3 semaphorins require neuropilins as co-receptors (84). The extracellular region of the plexin receptor has a sema domain (85) and its intracellular domain recruits the monomeric GTPase Rac1 and the Collapsin Response Mediator Proteins (CRMPs) (86). Semaphorins exist as both secreted and membrane-associated forms (87). They also have the sema domain, thus raising the possibility that these ligands and their receptors arose from a common ancestor (88). This ligand-receptor pair, much like the RTKs, spans the spectrum of interactions from direct cell-to-cell adhesion signaling by GPI-linked ligands to signaling by soluble ligands.
As seen with several other members of this recruiter group of receptors, plexins also exhibit receptor crosstalk. In epithelial cells, plexin B1 (the receptor for sema 4D) associates with Met, the RTK receptor for hepatocyte growth factor. Binding of sema 4D to plexin B1 induces tyrosine phosphorylation of both plexin B1 and Met; cells lacking Met do not respond to sema 4D (81). Class 4 semaphorins expressed in immune cells appear to activate other receptors (Tim-2) in addition to plexins (89).
Relevant reviews and publications:
82. H. Hu, T. F. Marton, C. S. Goodman, Plexin b mediates axon guidance in drosophila by simultaneously inhibiting active rac and enhancing rhoa signaling. Neuron 32, 39-51 (2001).
83. Z. He, K. C. Wang, V. Koprivica, G. Ming, H. J. Song, Knowing how to navigate: mechanisms of semaphorin signaling in the nervous system. Sci STKE 2002, RE1 (2002).
84. B. P. Liu, S. M. Strittmatter, Semaphorin-mediated axonal guidance via Rho-related G proteins. Curr Opin Cell Biol 13, 619-626 (2001).
85. H. Fujisawa, K. Ohta, T. Kameyama, Y. Murakami, Function of a cell adhesion molecule, plexin, in neuron network formation. Dev Neurosci 19, 101-105 (1997).
86. F. Nakamura, R. G. Kalb, S. M. Strittmatter, Molecular basis of semaphorin-mediated axon guidance. J Neurobiol 44, 219-229 (2000).
87. W. Schultze, V. Eulenburg, V. Lessmann, L. Herrmann, T. Dittmar, E. D. Gundelfinger, R. Heumann, K. S. Erdmann, Semaphorin4F interacts with the synapse-associated protein SAP90/PSD-95. J Neurochem 78, 482-489 (2001).
88. M. L. Winberg, J. N. Noordermeer, L. Tamagnone, P. M. Comoglio, M. K. Spriggs, M. Tessier-Lavigne, C. S. Goodman, Plexin A is a neuronal semaphorin receptor that controls axon guidance. Cell 95, 903-916 (1998).
89. A. Kumanogoh, S. Marukawa, K. Suzuki, N. Takegahara, C. Watanabe, E. Ch'ng, I. Ishida, H. Fujimura, S. Sakoda, K. Yoshida, et al., Class IV semaphorin Sema4A enhances T-cell activation and interacts with Tim-2. Nature 419, 629-633 (2002).