Biology Reference
In-Depth Information
Arp2/3 complex is an actin nucleating complex that binds to the sides of
existing actin filaments and nucleates a new filament at approximately a 70°
angle from the original filament ( Yang and Svitkina, 2011 ). Arp2/3 activity
thus results in a branched network of actin filaments and it is generally con-
sidered to mediate lamellipodial protrusion. However, a role for the Arp2/3
complex-mediated branched network has also been proposed in the forma-
tion of filopodia ( Yang and Svitkina, 2011 ; discussed further in Section 4.2 ).
The role of the Arp2/3 complex in the formation of minor processes, axons
and dendrites from neuronal cell bodies is not clear. Inhibition of Arp2/3
complex function through siRNA-mediated knock down of two com-
plex subunits (Arp3 and p34-Arc) in cultured hippocampal neurons did not
inhibit minor process formation, but rather it resulted in increased numbers
of minor process which, however, extended aberrantly ( Korobova and Svit-
kina, 2008 ). In a separate study, also using cultured hippocampal neurons,
the Arp2/3 complex was inhibited through the expression of a peptide that
prevents activation of the complex, which otherwise exhibits minimal base-
line activity in the absence of extracellular signals activating it ( Strasser et al.,
2004 ). In these experiments, inhibition of Apr2/3 complex function had
no effect on either axon formation or the number of dendrites per neuron.
Collectively, these studies indicate that the Apr2/3 complex has a minimal,
if any, role in the formation of minor processes from neuronal cell bodies.
Ena/VASP proteins are major regulators of actin filament barbed end
polymerization. One mechanism of action of Ena/VASP proteins is to act
as anticapping proteins. If the barbed end of a filament is capped by cap-
ping proteins, its polymerization will be impaired ( Menna et al., 2011 ).
Ena/VASP proteins thus may serve a role as local regulators of the capping
of filaments in discrete cellular domains. However, it is noteworthy that
Ena/VASP proteins may have additional functions to anticapping, possibly
including inhibition of Arp2/3-mediated filament branching, bundling of
actin filaments and other more controversial functions ( Bear and Gertler,
2009 ). Genetic deletion of Ena/VASP proteins in mice results in multiple
defects in brain cortical development including ectopias, improper layering
of the cortex and failure to form some major axon tracts ( Kwiatkowski et al.,
2007 ). In vitro analysis of minor process formation from Ena/VASP deleted
neurons provided insights into the role of these proteins in the formation
of filopodia, and revealed an unexpected complexity in the mechanisms
that can regulate filopodia formation from neuronal cell bodies ( Dent et al.,
2007 ). When cortical neurons lacking Ena/VASP were plated on a polyly-
sine substratum, they exhibited a striking deficit in minor process formation
Search WWH ::




Custom Search