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Concept
Netrin
Summary
Netrins are a class of proteins involved in axon guidance. They are named after the Sanskrit word "netr", which means "one who guides". Netrins are genetically conserved across nematode worms, fruit flies, frogs, mice, and humans. Structurally, netrin resembles the extracellular matrix protein laminin.
Netrins are chemotropic; a growing axon will either move towards or away from a higher concentration of netrin. Though the detailed mechanism of axon guidance is not fully understood, it is known that netrin attraction is mediated through UNC-40/DCC cell surface receptors and repulsion is mediated through UNC-5 receptors. Netrins also act as growth factors, encouraging cell growth activities in target cells. Mice deficient in netrin fail to form the hippocampal comissure or the corpus callosum.
A proposed model for netrin activity in the spinal column of developing human embryos is that netrins are released by the floor plate and then are picked up by receptor proteins embedded in the growth cones of axons belonging to neurons in the developing spinal column. The bodies of these neurons remain stationary while the axons follow a path defined by netrins, eventually connecting to neurons inside the embryonic brain by developing synapses. Research supports that new axons tend to follow previously traced pathways rather than being guided by netrins or related chemotropic factors.
Netrin was first described in the nematode Caenorhabditis elegans in 1990, and named UNC-6, according to standard C. elegans naming protocol. 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. As of 2009, five mammalian Netrins have been identified. Netrins 1, 3, and 4 are secreted proteins, whereas G1 and G2 are membrane bound proteins tethered by Glycophosphatidylinositol tails. All netrins discovered in invertebrates thus far are secreted.
The netrin family is composed mostly of secreted proteins which serve as bifunctional signals: attracting some neurons while repelling others during the development of the brain.
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