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User:Smaild2011/Netrin Proposal

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Netrin

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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

Netins 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


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

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