Slit-Robo

Slit-Robo is the name of a cell signaling protein complex with many diverse functions including axon guidance and angiogenesis.

Slit refers to a secreted protein that is most widely known as a repulsive axon guidance cue, and Robo refers to its transmembrane protein receptor. There are four different Robos and three Slits in vertebrates: Robo1, Robo2, Robo3/Rig-1, and Robo4, and Slit1, Slit2, Slit3.[1] There are three Robos and a single Slit in Drosophila. The corresponding Slit and Robo homologues in C. elegans are Slt and Sax-3, respectively.[2]

Slits are characterized by four distinct domains, each containing variable numbers of leucine-rich repeats (LRRs),[3] seven to nine EGF repeats,[4][5] an ALPS domain (Agrin, Perlecan, Laminin, Slit), and a cysteine knot.[6] Robos are characterized by five Ig-like domains, three fibronectin type III (FNIII) repeats, a transmembrane portion, and an intracellular tail with up to four conserved cytoplasmic motifs: CC0 (a potential site of tyrosine phosphorylation),[7] CC1 (also a potential site of tyrosine phosphorylation and binds P3 domain of netrin-1 receptor DCC),[8] CC2 (polyproline stretch; consensus binding site for Ena/Vasp proteins),[7] and CC3 (polyproline stretch).[9]

  1. ^ Yuan W, Zhou L, Chen JH, Wu JY, Rao Y, Ornitz DM (August 1999). "The mouse SLIT family: secreted ligands for ROBO expressed in patterns that suggest a role in morphogenesis and axon guidance". Dev. Biol. 212 (2): 290–306. doi:10.1006/dbio.1999.9371. PMID 10433822.
  2. ^ Zallen JA, Yi BA, Bargmann CI (January 1998). "The conserved immunoglobulin superfamily member SAX-3/Robo directs multiple aspects of axon guidance in C. elegans". Cell. 92 (2): 217–27. doi:10.1016/S0092-8674(00)80916-2. PMID 9458046.
  3. ^ Howitt JA, Clout NJ, Hohenester E (November 2004). "Binding site for Robo receptors revealed by dissection of the leucine-rich repeat region of Slit". EMBO J. 23 (22): 4406–12. doi:10.1038/sj.emboj.7600446. PMC 526463. PMID 15496984.
  4. ^ Rothberg JM, Hartley DA, Walther Z, Artavanis-Tsakonas S (December 1988). "slit: an EGF-homologous locus of D. melanogaster involved in the development of the embryonic central nervous system". Cell. 55 (6): 1047–59. doi:10.1016/0092-8674(88)90249-8. PMID 3144436. S2CID 9325118.
  5. ^ Rothberg JM, Jacobs JR, Goodman CS, Artavanis-Tsakonas S (December 1990). "slit: an extracellular protein necessary for development of midline glia and commissural axon pathways contains both EGF and LRR domains". Genes Dev. 4 (12A): 2169–87. doi:10.1101/gad.4.12a.2169. PMID 2176636.
  6. ^ Nguyen-Ba-Charvet KT, Chédotal A (2002). "Role of Slit proteins in the vertebrate brain". J. Physiol. Paris. 96 (1–2): 91–8. doi:10.1016/S0928-4257(01)00084-5. PMID 11755787. S2CID 21402002.
  7. ^ a b Bashaw GJ, Kidd T, Murray D, Pawson T, Goodman CS (June 2000). "Repulsive axon guidance: Abelson and Enabled play opposing roles downstream of the roundabout receptor". Cell. 101 (7): 703–15. doi:10.1016/S0092-8674(00)80883-1. PMID 10892742.
  8. ^ Stein E, Tessier-Lavigne M (March 2001). "Hierarchical organization of guidance receptors: silencing of netrin attraction by slit through a Robo/DCC receptor complex". Science. 291 (5510): 1928–38. Bibcode:2001Sci...291.1928S. doi:10.1126/science.1058445. PMID 11239147. S2CID 24626940. (Retracted, see doi:10.1126/science.adk1517,  Retraction Watch. If this is an intentional citation to a retracted paper, please replace {{retracted|...}} with {{retracted|...|intentional=yes}}.)
  9. ^ Kidd T, Brose K, Mitchell KJ, Fetter RD, Tessier-Lavigne M, Goodman CS, Tear G (January 1998). "Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors". Cell. 92 (2): 205–15. doi:10.1016/S0092-8674(00)80915-0. PMID 9458045.