Netrin 1

NTN1
Identifiers
Aliases	NTN1, NTN1L, netrin 1, MRMV4
External IDs	OMIM: 601614; MGI: 105088; HomoloGene: 21008; GeneCards: NTN1; OMA:NTN1 - orthologs
Available structures PDB Ortholog search: O95631 PDBe O95631 RCSB List of PDB id codes 4URT
Gene location (Human) Chr. Chromosome 17 (human) Band 17p13.1 Start 9,021,510 bp End 9,244,000 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11|11 B3 Start 68,100,190 bp End 68,291,649 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gastric mucosa right auricle of heart Descending thoracic aorta ascending aorta popliteal artery tibial arteries olfactory zone of nasal mucosa apex of heart parotid gland mucosa of esophagus Top expressed in Cerebral white matter tunica media of zone of aorta ankle joint ankle dermis ascending aorta vas deferens aortic valve atrium myocardium of ventricle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding Cellular component extracellular region cytoplasm basement membrane Biological process mammary gland duct morphogenesis positive regulation of cell motility axon guidance substrate-dependent cell migration, cell extension Cdc42 protein signal transduction positive regulation of axon extension inner ear morphogenesis negative regulation of axon extension apoptotic process mammary gland development positive regulation of cell population proliferation regulation of cell migration Ras protein signal transduction anterior/posterior axon guidance neuron migration axonogenesis nuclear migration cell-cell adhesion negative regulation of netrin-activated signaling pathway regulation of synapse assembly chemorepulsion of axon motor neuron axon guidance animal organ morphogenesis tissue development dendrite development Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9423 18208 Ensembl ENSG00000065320 ENSMUSG00000020902 UniProt H7BZF4 O95631 O09118 RefSeq (mRNA) NM_004822 NM_008744 RefSeq (protein) NP_004813 NP_032770 Location (UCSC) Chr 17: 9.02 – 9.24 Mb Chr 11: 68.1 – 68.29 Mb PubMed search
Wikidata
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Netrin-1 is a protein that in humans is encoded by the NTN1 gene.

Netrin is included in a family of laminin-related secreted proteins. The function of this gene has not yet been defined; however, netrin is thought to be involved in axon guidance and cell migration during development. Mutations and loss of expression of netrin suggest that variation in netrin may be involved in cancer development.

Interactions

NTN1 has been shown to interact with Deleted in Colorectal Cancer, and components of the extracellular matrix and the tumor microenvironment.

Midline crossing of commissural axons

During the development of the central nervous system, when the dorsal and ventral signaling is being established, the floor plate is an important site for crossing for groups of neural processes at the dorsal midline. Once crossed through the floor plate, these groups are now referred to as commissural axons. These neuronal cell bodies are signaled by Netrin 1 to be attracted to the floor plate from the dorsal half of the neural tube. NTN1 is a gene that encodes for the protein, Netrin-1. In a study done in knockout mice with a depletion of floor plate Netrin-1, it was shown that corticospinal axon tract midline crossing was disrupted. This study was done to show characteristics of patients with human congenital mirror movement disorder.

Afterwards, proper positioning of axons and midline crossing are pioneered by the Slit-Robo system where Slit proteins act as axonal repellents and Robo proteins (Robo-1, Robo-2, Robo-3) act in conjunction with Slit ligands to be their receptors. Slit with Robo-1 and Robo-2 repel axonal extension at the midline thereby commissural axons expressing Robo-3 cross the midline by interfering with Slit/Robo-1, Robo-2 repulsive activity. After crossing the floor plate, Robo-3 is downregulated and Slit/Robo-1, Robo-2 continue to express their repulsiveness at the midline. Furthermore, mutations in Robo-3 cause horizontal gaze palsy with progressive scoliosis.

Further reading

• Bouhidel JO, Wang P, Siu KL, Li H, Youn JY, Cai H (February 2015). "Netrin-1 improves post-injury cardiac function in vivo via DCC/NO-dependent preservation of mitochondrial integrity, while attenuating autophagy". Biochimica et Biophysica Acta. 1852 (2): 277–289. doi:10.1016/j.bbadis.2014.06.005. PMC 4262720. PMID 24928309.
• Arakawa H (December 2004). "Netrin-1 and its receptors in tumorigenesis". Nature Reviews. Cancer. 4 (12): 978–987. doi:10.1038/nrc1504. PMID 15573119. S2CID 867903.
• Mehlen P, Furne C (2006). "Netrin-1: when a neuronal guidance cue turns out to be a regulator of tumorigenesis". Cellular and Molecular Life Sciences. 62 (22): 2599–2616. doi:10.1007/s00018-005-5191-3. PMC 11139161. PMID 16158190. S2CID 29781275.
• Keino-Masu K, Masu M, Hinck L, Leonardo ED, Chan SS, Culotti JG, et al. (October 1996). "Deleted in Colorectal Cancer (DCC) encodes a netrin receptor". Cell. 87 (2): 175–185. doi:10.1016/S0092-8674(00)81336-7. PMID 8861902. S2CID 18468998.
• Serafini T, Colamarino SA, Leonardo ED, Wang H, Beddington R, Skarnes WC, et al. (December 1996). "Netrin-1 is required for commissural axon guidance in the developing vertebrate nervous system". Cell. 87 (6): 1001–1014. doi:10.1016/S0092-8674(00)81795-X. PMID 8978605. S2CID 1008380.
• Togari A, Mogi M, Arai M, Yamamoto S, Koshihara Y (September 2000). "Expression of mRNA for axon guidance molecules, such as semaphorin-III, netrins and neurotrophins, in human osteoblasts and osteoclasts". Brain Research. 878 (1–2): 204–209. doi:10.1016/S0006-8993(00)02700-1. PMID 10996153. S2CID 28322080.
• Corset V, Nguyen-Ba-Charvet KT, Forcet C, Moyse E, Chédotal A, Mehlen P (October 2000). "Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2b receptor". Nature. 407 (6805): 747–750. Bibcode:2000Natur.407..747C. doi:10.1038/35037600. PMID 11048721. S2CID 4423128.
• Manitt C, Colicos MA, Thompson KM, Rousselle E, Peterson AC, Kennedy TE (June 2001). "Widespread expression of netrin-1 by neurons and oligodendrocytes in the adult mammalian spinal cord". The Journal of Neuroscience. 21 (11): 3911–3922. doi:10.1523/JNEUROSCI.21-11-03911.2001. PMC 6762706. PMID 11356879.
• Srinivasan K, Strickland P, Valdes A, Shin GC, Hinck L (March 2003). "Netrin-1/neogenin interaction stabilizes multipotent progenitor cap cells during mammary gland morphogenesis". Developmental Cell. 4 (3): 371–382. doi:10.1016/S1534-5807(03)00054-6. PMID 12636918.
• Yebra M, Montgomery AM, Diaferia GR, Kaido T, Silletti S, Perez B, et al. (November 2003). "Recognition of the neural chemoattractant Netrin-1 by integrins alpha6beta4 and alpha3beta1 regulates epithelial cell adhesion and migration". Developmental Cell. 5 (5): 695–707. doi:10.1016/S1534-5807(03)00330-7. PMID 14602071.
• Mazelin L, Bernet A, Bonod-Bidaud C, Pays L, Arnaud S, Gespach C, et al. (September 2004). "Netrin-1 controls colorectal tumorigenesis by regulating apoptosis". Nature. 431 (7004): 80–84. Bibcode:2004Natur.431...80M. doi:10.1038/nature02788. PMID 15343335. S2CID 4417992.
• Kato HD, Kondoh H, Inoue T, Asanoma K, Matsuda T, Arima T, et al. (November 2004). "Expression of DCC and netrin-1 in normal human endometrium and its implication in endometrial carcinogenesis". Gynecologic Oncology. 95 (2): 281–289. doi:10.1016/j.ygyno.2004.07.050. PMID 15491747.
• Kruger RP, Lee J, Li W, Guan KL (2005). "Mapping netrin receptor binding reveals domains of Unc5 regulating its tyrosine phosphorylation". The Journal of Neuroscience. 24 (48): 10826–10834. doi:10.1523/JNEUROSCI.3715-04.2004. PMC 6730211. PMID 15574733.
• Hérincs Z, Corset V, Cahuzac N, Furne C, Castellani V, Hueber AO, et al. (April 2005). "DCC association with lipid rafts is required for netrin-1-mediated axon guidance". Journal of Cell Science. 118 (Pt 8): 1687–1692. doi:10.1242/jcs.02296. PMID 15811950.
• Kim TH, Lee HK, Seo IA, Bae HR, Suh DJ, Wu J, et al. (October 2005). "Netrin induces down-regulation of its receptor, Deleted in Colorectal Cancer, through the ubiquitin-proteasome pathway in the embryonic cortical neuron". Journal of Neurochemistry. 95 (1): 1–8. doi:10.1111/j.1471-4159.2005.03314.x. PMC 2683579. PMID 16181408.
• Ly NP, Komatsuzaki K, Fraser IP, Tseng AA, Prodhan P, Moore KJ, et al. (October 2005). "Netrin-1 inhibits leukocyte migration in vitro and in vivo". Proceedings of the National Academy of Sciences of the United States of America. 102 (41): 14729–14734. Bibcode:2005PNAS..10214729L. doi:10.1073/pnas.0506233102. PMC 1253572. PMID 16203981.
• Varadarajan, SG, Kong JH, Phan KD, Kao TJ, Panaitof SC, et al. (2017). "Netrin1 produced by neural progenitors, not floor plate cells, is required for axon guidance in the spinal cord". Neuron. 94 (4): 790–799. doi:10.1016/j.neuron.2017.03.007. PMC 5576449. PMID 28434801.

External links

• NTN1 human gene location in the UCSC Genome Browser.
• NTN1 human gene details in the UCSC Genome Browser.