User:Pmcronin/Netrin Proposal

Netrin

Netrins are a class of chemotropic proteins most famously known for their critical role in axonal guidance in the nervous system during embryo development. Evidence has shown these molecules to be genetically and functionally conserved across both invertebrates and vertebrate including nematode worms, fruitflies, frogs, and mice.

Discovery

C.elegans (1990) originally named UNC-6
First mammalian homologue was found in 1994 rodents
As of 2009 expression of 5 netrins has been discovered in mammals
Orthologs of the secreted netrin UNC-6 have since been identified in invertebrates other than C. elegans such as Drosophila melanogaster

Netrin was first described in the nematode Caenorhabditis elegans in 1990, and named UNC-6, according to standard C. elegans naming protocol.^[1] The first mammalian homologue of UNC-6 was discovered in 1994, where it was discovered to be a vital guidance cue for rodent commissural axons in the spinal cord.^[2] There are currently 5 types of Netrins identified in mammals. Netrins 1,3,and 4 are secreted proteins, whereas G1 and G2 are membrane bound proteins tethered by GPI tails.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768972/?tool=pubmed

Netrins and Receptors

Secreted Netrins (Netrin 1, 2, 3, 4)
(GPI)-anchored membrane proteins (Netrin G1 and Netrin-G2)
Netrin Receptors

Deleted in colorectal cancer (DCC) receptor
Down syndrome cell adhesion molecule (DSCAM) receptor
LAR tyrosine phosphatase receptor
Neogenin (NEO) receptor

Axonal Guidance

Growth Cone Navigation
Attraction and Repulsion of Specific Neurons
Plasticity of Axonal Guidance

Modulation by cyclic nucleotides
Local translation in the growth cone

Functions Outside Axonal Guidance

Role in Cancer

Deregulation
Targeted Anticancer Therapy

Netrin Deficiency

Dependance Receptors

Deletion leads to cancer or apoptosis

Netrin in Migration of Glial Precursor Cells

Many studies have shown that Netrin-1, UNC-40, UNC-6, and UNC-5 are involved in the migration of glia during embryogenesis.^[3] ^[4] ^[5]

Continued Research

References

Roles for Netrin signaling outside of axon guidance: a view from the worm

Moving around in a worm: netrin UNC-6 and circumferential axon guidance in C. elegans

Axon guidance: Netrin receptors are revealed

Netrin-1 and its receptors in tumorigenesis

The netrin protein family

Novel roles for Slits and netrins: axon guidance cues as anticancer targets?

Molecular Mechanisms of Axonal Guidance

Division of Labor Our group will meet regularly to divide the work and discuss any relevant information that is uncovered during the research phase of the project. By meeting regularly and presenting articles to each other, we will strengthen our understanding of the material and create a more cohesive and flowing contribution to wikipedia.

^ Hedgecock EM, Culotti JG, Hall DH. The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans. Neuron 1990;4:61-85
^ Serafini T, Kennedy TE, Galko MJ, Mirzayan C, Jessell TM, Tessier-Lavigne M. The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6. Cell 1994;78:409-424
^ Chen, H.; Wei, Q.; Zhang, J.; Xu, C.; Tan, T.; Ji, W. (19). "Netrin-1 signaling mediates NO-induced glial precursor migration and accumulation". Cell Research. 20 (2): 238–241. doi:10.1038/cr.2010.7. PMID 20084084. {{cite journal}}: Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |month= ignored (help)
^ von Hilchen, C. M.; Hein, I.; Technau, G. M.; Altenhein, B. (2010). "Netrins guide migration of distinct glial cells in the Drosophila embryo". Development. 137 (8): 1251–62. doi:10.1242/dev.042853. PMID 20223758. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: date and year (link)
^ Colón-Ramos, Daniel (5). "Glia Promote Local Synaptogenesis Through UNC-6 (Netrin) Signaling in C. elegans". Science. 318 (5847): 103–106. doi:10.1126 (inactive 2023-08-02). {{cite journal}}: Check |doi= value (help); Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)CS1 maint: DOI inactive as of August 2023 (link)

[1] Hedgecock EM, Culotti JG, Hall DH. The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans. Neuron 1990;4:61-85

[2] Serafini T, Kennedy TE, Galko MJ, Mirzayan C, Jessell TM, Tessier-Lavigne M. The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6. Cell 1994;78:409-424

[3] Chen, H.; Wei, Q.; Zhang, J.; Xu, C.; Tan, T.; Ji, W. (19). "Netrin-1 signaling mediates NO-induced glial precursor migration and accumulation". Cell Research. 20 (2): 238–241. doi:10.1038/cr.2010.7. PMID 20084084. {{cite journal}}: Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |month= ignored (help)

[4] von Hilchen, C. M.; Hein, I.; Technau, G. M.; Altenhein, B. (2010). "Netrins guide migration of distinct glial cells in the Drosophila embryo". Development. 137 (8): 1251–62. doi:10.1242/dev.042853. PMID 20223758. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: date and year (link)

[5] Colón-Ramos, Daniel (5). "Glia Promote Local Synaptogenesis Through UNC-6 (Netrin) Signaling in C. elegans". Science. 318 (5847): 103–106. doi:10.1126 (inactive 2023-08-02). {{cite journal}}: Check |doi= value (help); Check date values in: |date= and |year= / |date= mismatch (help); Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)CS1 maint: DOI inactive as of August 2023 (link)

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