Actin regulating proteins
Basically the actin dynamics are regulated by actin nucleating, severing, branching and bundling proteins.
Actin nucleating proteins are Arp 2/3 complex (Lamellipodia) and formins (Filopodia). The Arp 2/3 complex is also very important in the formation of Filopodia as well as dispensable for actin organization in neuronal growth cones.
Growth cone dynamics regulators (directly modulate actin dynamics):
- WAVE (wiskott Aldrich syndrome protein [WASP] family verprolin homologous protein)
- Ena/VASP (Vasodilator stimulated phosphoprotein)
- Profilin
- ADF (actin depolymerization factor)/ cofilin
WAVE protein is localized in the Lamellipodia and is part of the WAVE complex of the proteins that act together to regulate actin polymerization in Lamellipodia. Basically the WAVE pathway regulates the actin polymerization through the Arp 2/3 or Profilin and promotes axon growth.
A component of WAVE complex called Nap 1 (Nck associated protein 1) which is important in cortical neuronal differentiation as well as proper extension of axon.
The Ena/VASP proteins are localized at the tips of the Lamellipodia and Filopodia, which will accelerate the actin polymerization by their anticapping activity and bundle actin filaments. Absence of these proteins will lead to aberrant actin bundling and failure of Filopodia formation. Therefore formation of neurites in the absences of these proteins is not possible, hence it’s considered important in the neuron formation.
The role of Ena/ VASP signaling in axon formation appears to be conserved throughout the species. Additionally, Ena/VASP proteins recruit the actin regulator profilin, but the physiological relevance of this interaction is still not clear.
Profilin localizes to the leading edges of the growth cones and enhances the formatting of ATP bound G actin monomers that are incorporated into actin barbed ends. Ablation of isoform Profilin IIa protein leads to destabilization of actin cytoskeleton as well as increased in the number and length of the neurites.
But it was investigated in the Profilin Knockout mice, that polarization has taken place normally. It shows that Profilin I is compensating the function of Profilin II, But Profilin I knockout mice are embryonical lethal.
Cofilin is an actin severing proteins which are also implicated in the neuronal polarity. ADF and cofilin І which are expressed in brain is found to be abundant in the neuronal growth cones. They bind mostly to the ADP-actin rather than ATP actin which results in their association with the pointed end of actin filaments and promoting actin depolymerization. Both the proteins are regulated by Phosphorylation and phosphorylated form is mostly abundant in the cellular forms. The cofilin proteins are active during axonal growth cones compared to non growing future dendritic growth cones.
Microtubule regulating proteins
CLIP (Cytoplasmic linker proteins) and CLASPs (CLIP associated proteins) regulated the microtubule dynamics. They act as MT growth promoting and also MT stabilizing protein.
CRMP 2 (collapsin response mediator protein 2) binds to the free tubulin and promotes their capacity to bind to the microtubules. CRMP2 is inhibited by GSK 3β Phosphorylation and PTEN. WAVE complex helps the transportation CRMP2 on kinesin molecule.
Stathmin/Op18 is the MT destabilizing proteins, which can be inactivated inorder to attain MT stability and is necessary for the specification of the nascent axon.
1 comments:
<3
Post a Comment