| Structural highlights
Function
[PLXA3_MOUSE] Coreceptor for SEMA3A and SEMA3F. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance in the developing nervous system. Regulates the migration of sympathetic neurons, but not of neural crest precursors. Required for normal dendrite spine morphology in pyramidal neurons. May play a role in regulating semaphorin-mediated programmed cell death in the developing nervous system. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.[1] [2] [3] [4] [5] [6]
Evolutionary Conservation
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Publication Abstract from PubMed
Plexin cell surface receptors bind to semaphorin ligands and transduce signals for regulating neuronal axon guidance. The intracellular region of plexins is essential for signaling and contains a R-Ras/M-Ras GTPase activating protein (GAP) domain that is divided into two segments by a Rho GTPase-binding domain (RBD). The regulation mechanisms for plexin remain elusive, although it is known that activation requires both binding of semaphorin to the extracellular region and a Rho-family GTPase (Rac1 or Rnd1) to the RBD. Here we report the crystal structure of the plexin A3 intracellular region. The structure shows that the N- and C-terminal portions of the GAP homologous regions together form a GAP domain with an overall fold similar to other Ras GAPs. However, the plexin GAP domain adopts a closed conformation and cannot accommodate R-Ras/M-Ras in its substrate-binding site, providing a structural basis for the autoinhibited state of plexins. A comparison with the plexin B1 RBD/Rnd1 complex structure suggests that Rnd1 binding alone does not induce a conformational change in plexin, explaining the requirement of both semaphorin and a Rho GTPase for activation. The structure also identifies an N-terminal segment that is important for regulation. Both the N-terminal segment and the RBD make extensive interactions with the GAP domain, suggesting the presence of an allosteric network connecting these three domains that integrates semaphorin and Rho GTPase signals to activate the GAP. The importance of these interactions in plexin signaling is shown by both cell-based and in vivo axon guidance assays.
Crystal structure of the plexin A3 intracellular region reveals an autoinhibited conformation through active site sequestration.,He H, Yang T, Terman JR, Zhang X Proc Natl Acad Sci U S A. 2009 Aug 26. PMID:19717441[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Cheng HJ, Bagri A, Yaron A, Stein E, Pleasure SJ, Tessier-Lavigne M. Plexin-A3 mediates semaphorin signaling and regulates the development of hippocampal axonal projections. Neuron. 2001 Oct 25;32(2):249-63. PMID:11683995
- ↑ Waimey KE, Huang PH, Chen M, Cheng HJ. Plexin-A3 and plexin-A4 restrict the migration of sympathetic neurons but not their neural crest precursors. Dev Biol. 2008 Mar 15;315(2):448-58. doi: 10.1016/j.ydbio.2008.01.002. Epub 2008 , Jan 16. PMID:18262512 doi:http://dx.doi.org/10.1016/j.ydbio.2008.01.002
- ↑ Schwarz Q, Waimey KE, Golding M, Takamatsu H, Kumanogoh A, Fujisawa H, Cheng HJ, Ruhrberg C. Plexin A3 and plexin A4 convey semaphorin signals during facial nerve development. Dev Biol. 2008 Dec 1;324(1):1-9. doi: 10.1016/j.ydbio.2008.08.020. Epub 2008 Sep , 3. PMID:18804103 doi:http://dx.doi.org/10.1016/j.ydbio.2008.08.020
- ↑ Ben-Zvi A, Manor O, Schachner M, Yaron A, Tessier-Lavigne M, Behar O. The Semaphorin receptor PlexinA3 mediates neuronal apoptosis during dorsal root ganglia development. J Neurosci. 2008 Nov 19;28(47):12427-32. doi: 10.1523/JNEUROSCI.3573-08.2008. PMID:19020035 doi:http://dx.doi.org/10.1523/JNEUROSCI.3573-08.2008
- ↑ He H, Yang T, Terman JR, Zhang X. Crystal structure of the plexin A3 intracellular region reveals an autoinhibited conformation through active site sequestration. Proc Natl Acad Sci U S A. 2009 Aug 26. PMID:19717441
- ↑ Tran TS, Rubio ME, Clem RL, Johnson D, Case L, Tessier-Lavigne M, Huganir RL, Ginty DD, Kolodkin AL. Secreted semaphorins control spine distribution and morphogenesis in the postnatal CNS. Nature. 2009 Dec 24;462(7276):1065-9. doi: 10.1038/nature08628. Epub 2009 Dec 13. PMID:20010807 doi:http://dx.doi.org/10.1038/nature08628
- ↑ He H, Yang T, Terman JR, Zhang X. Crystal structure of the plexin A3 intracellular region reveals an autoinhibited conformation through active site sequestration. Proc Natl Acad Sci U S A. 2009 Aug 26. PMID:19717441
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