Suppression of AMIGO3 promotes axon regeneration after spinal cord injury - Essay Example

A common receptor,Nogo-66 receptor (NgR1) binds the three myelin inhibitors and signals inhibition and the collapse of the growth cone through the RhoGTPase pathway (Victor,2005). This it does by being in association with two binding partners that transduces signal, LINGO-1 (leucine rich-repeat and immunoglobulin domain-containing, Nogo receptor interacting protein and p75 (the low affinity neutrophin receptor). The NgR1 andLINGO-1 are widely present in CNS neurons but the p75 presence is more restricted.

TROY is a TNT receptor member which is broadly expressed in a pattern in adult neurons and in postnatal (Berry, 1999). TROY is also a substitute for p75 in the NgR1/p75/LINGO-1 receptor complex. LINGO-1 like LRR motifs are also present in other proteins like amphoterin (also known as HMGBI) which is a heparin-binding LRR protein present in abundance in growth cones and amphoterin-induced gene and open reading frame (AMIGO), together with AMIGO2 and AMIGO3 are present in tissues of the of adult mice (Tayole,2006).

However AMIGO3 is much distributed widely as it is also found in the spleen, kidneys and in the liver .In the process of postnatal development there is correlation between AMIGO and the onset of CNS myelin which is localised in the fibre tracts of the axon. AMIGO-immunoglobulin fusion protein which is substrate bound antagonises AMIGO and also promotes the hippocampal neurons outgrowth in the neurite. However, not much is known about the properties of AMIGO2 and AMIGO3 in the axon (Suggate, 2009).

The levels of LINGO-1 expression in the spinal cord after a spinal cord injury do not increase until 14 days, this is because it is likely that during the critical stages after CNS injury other NgR1 co-receptors that mediate the inhibition of axon growth are expressed and are able to function (Shao, 2005). In the dorsal root ganglion neuron, (DRGN) and retinal ganglion cell (RGC) axotomy, model three occurrences are identified; (1) In the DRGN and RGC , there is significant and preferential increase of protein levels and AMIGO3 mRNA immediately after central axotomy; (2) there is correlation between depression of AMIGO3 expression together with dorsal column (DC) and the regeneration of optic nerve; .

In both transfected cells of rat and human brain lysates there is interaction between AMIGO3 with NgR1 and p75/TROY where they form a functional receptor complex which usually activates RhoGTP in the cells that are exposed to the CNS (Filbin,2003). AMIGO 3 AND HOW IT WORKS In the acute stage of spinal injury, LINGO-1 is substituted by AMIGO3 in centrally axotomized DRGN and RGC. Immediate responses to inhibition of axon growth to CNS myelin are mediated by the NgR1-p75/ TROY-AMIGO3 receptor complex (Read,2009).

As much as LINGO-1 is an agreed upon as co-receptor in the NgR1-p75/TROY receptor complex which signals inhibition of the CNS axon growth, its patterns of expression after an injury in the spinal cord are not in line with its proposed function (Jacques,2009). After the injury, LINGO-1 levels do not increase in an appreciable rate in the DRGN until after 14 days, therefore other molecules may contribute in signaling the axon growth in the acute stage of spinal injury (Rauvala,2010). AMIGO3 being a molecule related to regeneration, interacts with NgR1, p75 and TROYand together they form a functional receptor complex for ligands derived from the CNS myelin.

The ligands activate RhoA and controls growth of the axon and also its extension.