2v9s

Structural highlights

Function

[SLIT2_HUMAN] Thought to act as molecular guidance cue in cellular migration, and function appears to be mediated by interaction with roundabout homolog receptors. During neural development involved in axonal navigation at the ventral midline of the neural tube and projection of axons to different regions. SLIT1 and SLIT2 seem to be essential for midline guidance in the forebrain by acting as repulsive signal preventing inappropriate midline crossing by axons projecting from the olfactory bulb. In spinal chord development may play a role in guiding commissural axons once they reached the floor plate by modulating the response to netrin. In vitro, silences the attractive effect of NTN1 but not its growth-stimulatory effect and silencing requires the formation of a ROBO1-DCC complex. May be implicated in spinal chord midline post-crossing axon repulsion. In vitro, only commissural axons that crossed the midline responded to SLIT2. In the developing visual system appears to function as repellent for retinal ganglion axons by providing a repulsion that directs these axons along their appropriate paths prior to, and after passage through, the optic chiasm. In vitro, collapses and repels retinal ganglion cell growth cones. Seems to play a role in branching and arborization of CNS sensory axons, and in neuronal cell migration. In vitro, Slit homolog 2 protein N-product, but not Slit homolog 2 protein C-product, repels olfactory bulb (OB) but not dorsal root ganglia (DRG) axons, induces OB growth cones collapse and induces branching of DRG axons. Seems to be involved in regulating leukocyte migration.^{[1] [2] [3] [4] [5] [6]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Brose K, Bland KS, Wang KH, Arnott D, Henzel W, Goodman CS, Tessier-Lavigne M, Kidd T. Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance. Cell. 1999 Mar 19;96(6):795-806. PMID:10102268
2. ↑ Zou Y, Stoeckli E, Chen H, Tessier-Lavigne M. Squeezing axons out of the gray matter: a role for slit and semaphorin proteins from midline and ventral spinal cord. Cell. 2000 Aug 4;102(3):363-75. PMID:10975526
3. ↑ Niclou SP, Jia L, Raper JA. Slit2 is a repellent for retinal ganglion cell axons. J Neurosci. 2000 Jul 1;20(13):4962-74. PMID:10864954
4. ↑ Wu JY, Feng L, Park HT, Havlioglu N, Wen L, Tang H, Bacon KB, Jiang Zh, Zhang Xc, Rao Y. The neuronal repellent Slit inhibits leukocyte chemotaxis induced by chemotactic factors. Nature. 2001 Apr 19;410(6831):948-52. PMID:11309622 doi:http://dx.doi.org/10.1038/35073616
5. ↑ Nguyen Ba-Charvet KT, Brose K, Ma L, Wang KH, Marillat V, Sotelo C, Tessier-Lavigne M, Chedotal A. Diversity and specificity of actions of Slit2 proteolytic fragments in axon guidance. J Neurosci. 2001 Jun 15;21(12):4281-9. PMID:11404413
6. ↑ Stein E, Tessier-Lavigne M. Hierarchical organization of guidance receptors: silencing of netrin attraction by slit through a Robo/DCC receptor complex. Science. 2001 Mar 9;291(5510):1928-38. Epub 2001 Feb 8. PMID:11239147 doi:http://dx.doi.org/10.1126/science.1058445
7. ↑ Morlot C, Thielens NM, Ravelli RB, Hemrika W, Romijn RA, Gros P, Cusack S, McCarthy AA. Structural insights into the Slit-Robo complex. Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):14923-8. Epub 2007 Sep 11. PMID:17848514