User:Pmcronin/Netrin Proposal

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.