Netrin 1

Netrin-1 is a protein that in humans is encoded by the NTN1 gene.[5][6]

NTN1
Available structures
PDBOrtholog search: O95631 PDBe O95631 RCSB
Identifiers
AliasesNTN1, NTN1L, netrin 1, MRMV4
External IDsOMIM: 601614 MGI: 105088 HomoloGene: 21008 GeneCards: NTN1
Orthologs
SpeciesHumanMouse
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 MbChr 11: 68.1 – 68.29 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[6]

Interactions

NTN1 has been shown to interact with Deleted in Colorectal Cancer,[5][7] and components of the extracellular matrix and the tumor microenvironment.[8]

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.[9] 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.[10] 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.

References

  1. GRCh38: Ensembl release 89: ENSG00000065320 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000020902 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Meyerhardt JA, Caca K, Eckstrand BC, Hu G, Lengauer C, Banavali S, Look AT, Fearon ER (January 1999). "Netrin-1: interaction with deleted in colorectal cancer (DCC) and alterations in brain tumors and neuroblastomas". Cell Growth Differ. 10 (1): 35–42. PMID 9950216.
  6. "Entrez Gene: NTN1 netrin 1".
  7. Geisbrecht, Brian V; Dowd Kimberly A; Barfield Ronald W; Longo Patti A; Leahy Daniel J (Aug 2003). "Netrin binds discrete subdomains of DCC and UNC5 and mediates interactions between DCC and heparin". J. Biol. Chem. United States. 278 (35): 32561–8. doi:10.1074/jbc.M302943200. ISSN 0021-9258. PMID 12810718.
  8. Kryza D, Wischhusen J, Richaud M, Hervieu M, Sidi Boumedine J, Delcros JG, Besse S, Baudier T, Laval PA, Breusa S, Boutault E, Clermidy H, Rama N, Ducarouge B, Devouassoux-Shisheboran M, Chezal JM, Giraudet AL, Walter T, Mehlen P, Sarrut D, Gibert B.From netrin-1-targeted SPECT/CT to internal radiotherapy for management of advanced solid tumors. EMBO Mol Med. 2023 Apr 11;15(4):e16732. doi: 10.15252/emmm.202216732. Epub 2023 Mar 6. PMID: 36876343
  9. Pourchet, Oriane (Jan 19, 2021). "Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements". Cell Reports. 34 (3): 108654. doi:10.1016/j.celrep.2020.108654. hdl:10261/308989. PMID 33472083. S2CID 231663364.
  10. Blockus, Heike; Chedotal, Alain (Sep 1, 2016). "Slit-Robo signaling". Development. 143 (17): 3037–3044. doi:10.1242/dev.132829. PMID 27578174. S2CID 10315151.

Further reading

Varadarajan, Supraja G., et al. "Netrin1 produced by neural progenitors, not floor plate cells, is required for axon guidance in the spinal cord." Neuron 94.4 (2017): 790-799. https://doi.org/10.1016/j.neuron.2017.03.007


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