Structural highlights
Function
SLIT_DROME A short-range repellent, controlling axon crossing of the midline and a long-range chemorepellent, controlling mesoderm migration and patterning away from the midline. May interact with extracellular matrix molecules. Repulsive ligand for the guidance receptor roundabout (robo) and prevents inappropriate midline crossing by Robo-expressing axons.[1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Recognition of the large secreted protein Slit by receptors of the Robo family provides fundamental signals in axon guidance and other developmental processes. In Drosophila, Slit-Robo signalling regulates midline crossing and the lateral position of longitudinal axon tracts. We report the functional dissection of Drosophila Slit, using structure analysis, site-directed mutagenesis and in vitro assays. The N-terminal region of Slit consists of a tandem array of four independently folded leucine-rich repeat (LRR) domains, connected by disulphide-tethered linkers. All three Drosophila Robos were found to compete for a single highly conserved site on the concave face of the second LRR domain of Slit. We also found that this domain is sufficient for biological activity in a chemotaxis assay. Other Slit activities may require Slit dimerisation mediated by the fourth LRR domain. Our results show that a small portion of Slit is able to induce Robo signalling and indicate that the distinct functions of Drosophila Robos are encoded in their divergent cytosolic domains.
Binding site for Robo receptors revealed by dissection of the leucine-rich repeat region of Slit.,Howitt JA, Clout NJ, Hohenester E EMBO J. 2004 Nov 10;23(22):4406-12. Epub 2004 Oct 21. PMID:15496984[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rothberg JM, Jacobs JR, Goodman CS, Artavanis-Tsakonas S. slit: an extracellular protein necessary for development of midline glia and commissural axon pathways contains both EGF and LRR domains. Genes Dev. 1990 Dec;4(12A):2169-87. PMID:2176636
- ↑ Kidd T, Bland KS, Goodman CS. Slit is the midline repellent for the robo receptor in Drosophila. Cell. 1999 Mar 19;96(6):785-94. PMID:10102267
- ↑ Rothberg JM, Hartley DA, Walther Z, Artavanis-Tsakonas S. slit: an EGF-homologous locus of D. melanogaster involved in the development of the embryonic central nervous system. Cell. 1988 Dec 23;55(6):1047-59. PMID:3144436
- ↑ 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
- ↑ Howitt JA, Clout NJ, Hohenester E. Binding site for Robo receptors revealed by dissection of the leucine-rich repeat region of Slit. EMBO J. 2004 Nov 10;23(22):4406-12. Epub 2004 Oct 21. PMID:15496984
