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Gene Review

SLIT3  -  slit homolog 3 (Drosophila)

Homo sapiens

Synonyms: KIAA0814, MEGF5, Multiple EGF-like domains protein 5, Multiple epidermal growth factor-like domains protein 5, SLIL2, ...
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Disease relevance of SLIT3

  • In primary tumours, SLIT3 was methylated in 16% of primary breast tumours, 35% of gliomas and 38% of colorectal tumours [1].
  • SLIT2 and SLIT3 mRNAs were co-expressed in embryonic stem (ES) cells with embryoid body formation, and diffuse type gastric cancer with signet ring cell features [2].
  • In contrast, the expression of slit2 mRNA increased in most of the malignant mammary tumors, and an increase in slit3 mRNA expression was observed in 2 of the malignant mixed tumors [3].
  • Inhibition of medulloblastoma cell invasion by Slit [4].
  • SLIT1 mRNA was expressed in fetal brain, infant brain, anaplastic oligodendroglioma, and Jurkat T cells [2].

Psychiatry related information on SLIT3

  • A recent report suggested SLITRK1 (Slit and Trk-like 1) as a candidate gene for Tourette Syndrome (TS) [5].
  • Compared with the Dilated group, the Slit-like group showed significantly rapid deterioration into lethargy after shunt obstruction [6].

High impact information on SLIT3

  • Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway [7].
  • The Slit protein guides neuronal and leukocyte migration through the transmembrane receptor Roundabout (Robo) [7].
  • Outgrowing axons are routed towards the hippocampal formation by specific expression of long-range cues, which include secreted class 3 semaphorins, netrin 1 and Slit proteins [8].
  • Here, using genetics, biochemistry, and cell biology, we demonstrate that Sos is recruited to the plasma membrane, where it forms a ternary complex with the Roundabout receptor and the SH3-SH2 adaptor protein Dreadlocks (Dock) to regulate Rac-dependent cytoskeletal rearrangement in response to the Slit ligand [9].
  • (2002 [this issue of Neuron]) demonstrate that in addition to their roles in axon guidance and cell migration cue, Slit proteins can also regulate dendritic growth [10].

Chemical compound and disease context of SLIT3

  • AIMS: To assess the effects of (1) mydriasis and (2) single versus three field photography on screening for diabetic eye disease using digital photography METHOD: Slit lamp examination findings were compared to digital fundal photographs for the detection of any retinopathy and for referable retinopathy in 398 patients (794 eyes) [11].
  • Re: Slit grafting: the use of serrated island grafts in male and female-pattern alopecia. J Dermatol Surg Oncol 1991;17:243-53 [12].

Biological context of SLIT3


Anatomical context of SLIT3

  • SLIT3 was found to be methylated in 12 out of 29 (41%) of breast, one out of 15 (6.7%) lung, two out of six (33%) colorectal and in two out of (29%) glioma tumour cell lines [1].
  • Dual trafficking of Slit3 to mitochondria and cell surface demonstrates novel localization for Slit protein [14].
  • In the present study, we observe that both Slit1 and Slit3 repel and inhibit neurite growth of fetal DA neurons [15].
  • In humans, slit2 protein attracts endothelial cells and promotes tube formation in the tumor angiogenic mechanism [3].
  • These results suggest that the expression of slit2 plays an important role in tumor angiogenesis in canine mammary gland tumors and that slit2 can be a putative marker for malignancy diagnosis of these tumors [3].

Associations of SLIT3 with chemical compounds


Other interactions of SLIT3


Analytical, diagnostic and therapeutic context of SLIT3

  • However, unlike fetal DA neurites, no directed neurite outgrowth was observed in the cocultures of ES-derived DA neurons with Netrin-1-, Slit1-, and Slit3-producing cells [15].
  • Analytical gel filtration chromatography demonstrates that Slit D2 associates with a soluble Robo fragment and a heparin-derived oligosaccharide to form a ternary complex [16].
  • Co-transfection of 293 cells with Slit and glypican-1 cDNAs followed by immunoprecipitation demonstrated that these interactions also occur in vivo, and immunocytochemical studies showed colocalization in the embryonic and adult central nervous system [18].
  • In conclusion, we report an altered expression and redistribution of Robo2 and Slit1 in the DRG and sciatic nerve trunk after peripheral axotomy [20].
  • By contrast, injury to the central axons of the DRG by dorsal rhizotomy did not up-regulate Slit1 and Robo2 expression [20].


  1. Epigenetic inactivation of SLIT3 and SLIT1 genes in human cancers. Dickinson, R.E., Dallol, A., Bieche, I., Krex, D., Morton, D., Maher, E.R., Latif, F. Br. J. Cancer (2004) [Pubmed]
  2. Comparative genomics on SLIT1, SLIT2, and SLIT3 orthologs. Katoh, Y., Katoh, M. Oncol. Rep. (2005) [Pubmed]
  3. Expression Patterns of the slit Subfamily mRNA in Canine Malignant Mammary Tumors. Tanno, T., Tanaka, Y., Sugiura, T., Akiyoshi, H., Takenaka, S., Kuwamura, M., Yamate, J., Ohashi, F., Kubo, K., Tsuyama, S. J. Vet. Med. Sci. (2006) [Pubmed]
  4. Inhibition of medulloblastoma cell invasion by Slit. Werbowetski-Ogilvie, T.E., Seyed Sadr, M., Jabado, N., Angers-Loustau, A., Agar, N.Y., Wu, J., Bjerkvig, R., Antel, J.P., Faury, D., Rao, Y., Del Maestro, R.F. Oncogene (2006) [Pubmed]
  5. Overrepresentation of rare variants in a specific ethnic group may confuse interpretation of association analyses. Keen-Kim, D., Mathews, C.A., Reus, V.I., Lowe, T.L., Herrera, L.D., Budman, C.L., Gross-Tsur, V., Pulver, A.E., Bruun, R.D., Erenberg, G., Naarden, A., Sabatti, C., Freimer, N.B. Hum. Mol. Genet. (2006) [Pubmed]
  6. Clinical significance of ventricular size in shunted-hydrocephalic children. Sakamoto, H., Kitano, S., Nishikawa, M., Fujitani, K. Acta Neurochir. Suppl. (1998) [Pubmed]
  7. Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway. Wong, K., Ren, X.R., Huang, Y.Z., Xie, Y., Liu, G., Saito, H., Tang, H., Wen, L., Brady-Kalnay, S.M., Mei, L., Wu, J.Y., Xiong, W.C., Rao, Y. Cell (2001) [Pubmed]
  8. New molecules for hippocampal development. Skutella, T., Nitsch, R. Trends Neurosci. (2001) [Pubmed]
  9. Son of sevenless directly links the robo receptor to rac activation to control axon repulsion at the midline. Yang, L., Bashaw, G.J. Neuron (2006) [Pubmed]
  10. Conserved cues for axon and dendrite growth in the developing cortex. McAllister, A.K. Neuron (2002) [Pubmed]
  11. Effect of mydriasis and different field strategies on digital image screening of diabetic eye disease. Murgatroyd, H., Ellingford, A., Cox, A., Binnie, M., Ellis, J.D., MacEwen, C.J., Leese, G.P. The British journal of ophthalmology. (2004) [Pubmed]
  12. Re: Slit grafting: the use of serrated island grafts in male and female-pattern alopecia. J Dermatol Surg Oncol 1991;17:243-53. Cohen, I.S. The Journal of dermatologic surgery and oncology. (1991) [Pubmed]
  13. CpG island methylation and expression of tumour-associated genes in lung carcinoma. Dammann, R., Strunnikova, M., Schagdarsurengin, U., Rastetter, M., Papritz, M., Hattenhorst, U.E., Hofmann, H.S., Silber, R.E., Burdach, S., Hansen, G. Eur. J. Cancer (2005) [Pubmed]
  14. Dual trafficking of Slit3 to mitochondria and cell surface demonstrates novel localization for Slit protein. Little, M.H., Wilkinson, L., Brown, D.L., Piper, M., Yamada, T., Stow, J.L. Am. J. Physiol., Cell Physiol. (2001) [Pubmed]
  15. Axonal growth regulation of fetal and embryonic stem cell-derived dopaminergic neurons by netrin-1 and slits. Lin, L., Isacson, O. Stem Cells (2006) [Pubmed]
  16. A molecular mechanism for the heparan sulfate dependence of slit-robo signaling. Hussain, S.A., Piper, M., Fukuhara, N., Strochlic, L., Cho, G., Howitt, J.A., Ahmed, Y., Powell, A.K., Turnbull, J.E., Holt, C.E., Hohenester, E. J. Biol. Chem. (2006) [Pubmed]
  17. Long-lasting effects of sublingual immunotherapy for house dust mites in allergic rhinitis with bronchial hyperreactivity: a long-term (13-year) retrospective study in real life. Marogna, M., Bruno, M., Massolo, A., Falagiani, P. Int. Arch. Allergy Immunol. (2007) [Pubmed]
  18. Characterization of Slit protein interactions with glypican-1. Ronca, F., Andersen, J.S., Paech, V., Margolis, R.U. J. Biol. Chem. (2001) [Pubmed]
  19. Multiple dosing of prostaglandin F2 alpha or epinephrine on cynomolgus monkey eyes. II. Slit-lamp biomicroscopy, aqueous humor analysis, and fluorescein angiography. Camras, C.B., Bhuyan, K.C., Podos, S.M., Bhuyan, D.K., Master, R.W. Invest. Ophthalmol. Vis. Sci. (1987) [Pubmed]
  20. Dynamic changes in Robo2 and Slit1 expression in adult rat dorsal root ganglion and sciatic nerve after peripheral and central axonal injury. Yi, X.N., Zheng, L.F., Zhang, J.W., Zhang, L.Z., Xu, Y.Z., Luo, G., Luo, X.G. Neurosci. Res. (2006) [Pubmed]
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