ROBO1 explained

Roundabout homolog 1 is a protein that in humans is encoded by the ROBO1 gene.^{[1] [2] [3]}

Function

Bilateral symmetric nervous systems have special midline structures that establish a partition between the two mirror image halves. Some axons project toward and across the midline in response to long-range chemoattractants emanating from the midline. The protein encoded by ROBO1 is structurally similar to a Drosophila integral membrane protein which is encoded by the Drosophila roundabout gene (a member of the immunoglobulin gene superfamily) and is both an axon guidance receptor and a cell adhesion receptor, known to be involved in the decision by axons to cross the central nervous system midline. Two transcript variants encoding different isoforms have been found for ROBO1.

Clinical significance

ROBO1 was implicated in a communication disorder based on a Finnish pedigree with severe dyslexia. Analyses revealed a translocation had occurred disrupting ROBO1.^[4] Study of the phonological memory component of the language acquisition system suggests that ROBO1 polymorphisms are associated with functioning in this system.^[5] The gene is thought to be related to the brain's ability to represent quantities, and is correlated with better math scores of young children in one limited study.^[6]

Further reading

• Sundaresan V, Chung G, Heppell-Parton A, etal . Homozygous deletions at 3p12 in breast and lung cancer . Oncogene . 17 . 13 . 1723–9 . 1998 . 9796701 . 10.1038/sj.onc.1202103 . free .
• Zhao XC, Zhang LM, Li Q, Tong DY, Fan LC, An P, Wu XY, Chen WM, Zhao P, Wang J . Isoflurane post-conditioning protects primary cultures of cortical neurons against oxygen and glucose deprivation injury via upregulation of Slit2/Robo1. . Brain Res. . 1537 . 283–9 . 2013 . 23994690 . 10.1016/j.brainres.2013.08.036 . 3820100.
• Brose K, Bland KS, Wang KH, etal . Slit proteins bind Robo receptors and have an evolutionarily conserved role in repulsive axon guidance . Cell . 96 . 6 . 795–806 . 1999 . 10102268 . 10.1016/S0092-8674(00)80590-5 . 16301178 . free .
• Yuan W, Zhou L, Chen JH, etal . 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 . 1999 . 10433822 . 10.1006/dbio.1999.9371 . free .
• Bashaw GJ, Kidd T, Murray D, etal . Repulsive axon guidance: Abelson and Enabled play opposing roles downstream of the roundabout receptor . Cell . 101 . 7 . 703–15 . 2000 . 10892742 . 10.1016/S0092-8674(00)80883-1 . 2715852 . free .
• Nguyen Ba-Charvet KT, Brose K, Ma L, etal . Diversity and specificity of actions of Slit2 proteolytic fragments in axon guidance . J. Neurosci. . 21 . 12 . 4281–9 . 2001 . 11404413 . 10.1523/JNEUROSCI.21-12-04281.2001. 6762758 . free .
• Wong K, Ren XR, Huang YZ, etal . Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway . Cell . 107 . 2 . 209–21 . 2001 . 11672528 . 10.1016/S0092-8674(01)00530-X . 2458943 . free .
• Dallol A, Forgacs E, Martinez A, etal . Tumour specific promoter region methylation of the human homologue of the Drosophila Roundabout gene DUTT1 (ROBO1) in human cancers . Oncogene . 21 . 19 . 3020–8 . 2002 . 12082532 . 10.1038/sj.onc.1205421 . free .
• Latil A, Chêne L, Cochant-Priollet B, etal . Quantification of expression of netrins, slits and their receptors in human prostate tumors . Int. J. Cancer . 103 . 3 . 306–15 . 2003 . 12471613 . 10.1002/ijc.10821 . 22859295 . free .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Hivert B, Liu Z, Chuang CY, etal . Robo1 and Robo2 are homophilic binding molecules that promote axonal growth . Mol. Cell. Neurosci. . 21 . 4 . 534–45 . 2003 . 12504588 . 10.1006/mcne.2002.1193 . 19664833 .
• Wang B, Xiao Y, Ding BB, etal . Induction of tumor angiogenesis by Slit-Robo signaling and inhibition of cancer growth by blocking Robo activity . Cancer Cell . 4 . 1 . 19–29 . 2004 . 12892710 . 10.1016/S1535-6108(03)00164-8 . free .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Hannula-Jouppi K, Kaminen-Ahola N, Taipale M, etal . The axon guidance receptor gene ROBO1 is a candidate gene for developmental dyslexia . PLOS Genet. . 1 . 4 . e50 . 2006 . 16254601 . 10.1371/journal.pgen.0010050 . 1270007 . free .
• Werbowetski-Ogilvie TE, Seyed Sadr M, Jabado N, etal . Inhibition of medulloblastoma cell invasion by Slit . Oncogene . 25 . 37 . 5103–12 . 2006 . 16636676 . 10.1038/sj.onc.1209524 . 2072874 .
• Muzny DM, Scherer SE, Kaul R, etal . The DNA sequence, annotation and analysis of human chromosome 3 . Nature . 440 . 7088 . 1194–8 . 2006 . 16641997 . 10.1038/nature04728 . 2006Natur.440.1194M . free .
• Gröne J, Doebler O, Loddenkemper C, etal . Robo1/Robo4: differential expression of angiogenic markers in colorectal cancer . Oncol. Rep. . 15 . 6 . 1437–43 . 2007 . 16685377 . 10.3892/or.15.6.1437. free .
• Ito H, Funahashi S, Yamauchi N, etal . Identification of ROBO1 as a novel hepatocellular carcinoma antigen and a potential therapeutic and diagnostic target . Clin. Cancer Res. . 12 . 11 Pt 1 . 3257–64 . 2007 . 16740745 . 10.1158/1078-0432.CCR-05-2787 . free .

Notes and References

1. Kidd T, Brose K, Mitchell KJ, Fetter RD, Tessier-Lavigne M, Goodman CS, Tear G . Roundabout controls axon crossing of the CNS midline and defines a novel subfamily of evolutionarily conserved guidance receptors . Cell . 92 . 2 . 205–15 . Feb 1998 . 9458045 . 10.1016/S0092-8674(00)80915-0 . 2036419 . free .
2. Sundaresan V, Roberts I, Bateman A, Bankier A, Sheppard M, Hobbs C, Xiong J, Minna J, Latif F, Lerman M, Rabbitts P . The DUTT1 gene, a novel NCAM family member is expressed in developing murine neural tissues and has an unusually broad pattern of expression . Mol Cell Neurosci . 11 . 1–2 . 29–35 . Aug 1998 . 9608531 . 10.1006/mcne.1998.0672 . 7168171 .
3. Web site: Entrez Gene: ROBO1 roundabout, axon guidance receptor, homolog 1 (Drosophila).
4. Hannula-Jouppi K, Kaminen-Ahola N, Taipale M, Eklund R, Nopola-Hemmi J, Kääriäinen H, Kere J . The axon guidance receptor gene ROBO1 is a candidate gene for developmental dyslexia . PLOS Genet. . 1 . 4 . e50 . October 2005 . 16254601 . 1270007 . 10.1371/journal.pgen.0010050 . free .
5. Bates TC, Luciano M, Medland SE, Montgomery GW, Wright MJ, Martin NG . Genetic variance in a component of the language acquisition device: ROBO1 polymorphisms associated with phonological buffer deficits . Behav. Genet. . 41 . 1 . 50–7 . January 2011 . 20949370 . 10.1007/s10519-010-9402-9 . 13129473 .
6. Web site: How genetic variation gives rise to differences in mathematical ability.