Actin Isoforms in Neuronal Development and Function - International Review of Cell and Molecular Biology - page 158

integrate into complex synaptic circuits, the actin cytoskeleton within den-
dritic spines drives the postsynaptic remodeling required for synaptic plas-
ticity, learning, and memory ( Cingolani and Goda, 2008 ). Throughout all
these cellular events, the dynamic polymerization and remodeling of actin
filaments serves to form molecular scaffolds, promote vesicular transport,
and induce membrane remodeling as well as a myriad of other functions.
Collectively, these actin-driven processes facilitate neuronal morphological
changes that are required for the proper development and function of the
nervous system. Actin dynamics have also been implicated in the regulation
of gene expression, extending the reach of actin into the nucleus ( Visa and
Percipalle, 2010 ). Considering these widespread functions, it is perhaps not
so surprising that the neuronal actin cytoskeleton is composed of multiple,
distinct actin isoforms.
3. ACTIN ISOFORMS
The mammalian genome contains six different actin isoforms encoded
by six distinct genes ( Vandekerckhove and Weber, 1978 ). The actin isoforms
were initially discovered based on their differential mobility following iso-
electric focusing, which resulted in the migration of three distinct spots
of actin: α-actin, the most negatively charged/acidic, followed by β-actin
and the most positively charged/basic γ-actin. Within these three general
isotypes, there are three α-actin isoforms named for where they are predom-
inantly expressed including α-skeletal, α-cardiac, and α-smooth actin for
skeletal, cardiac, and smooth muscles, respectively. Along with β-cytoplasmic
actin, the two forms of γ-actin, γ-smooth and γ-cytoplasmic actin, round
out the remaining members of the mammalian actin isoform family.
Interestingly, no actin isoform differs from another by more than 7% at
the primary amino acid sequence level. The two most similar actin isoforms,
β-cytoplasmic and γ-cytoplasmic actin, differ at only four out of 375 amino
acids clustered at the N-terminus ( Fig. 4.1 ). Even more striking is that
the amino acid substitutions between β- and γ-cytoplasmic actin are bio-
chemically conservative, with aspartic acid substituted for glutamic acid at
positions one through three, and valine substituted for isoleucine at posi-
tion 10 in γ-actin compared to β-actin. Actin isoform primary amino acid
sequences are completely conserved from birds to mammals, suggesting that
selective pressures have maintained these actin isoforms through 300 mil-
lion of years of evolution and that they likely serve at least some nonover-
lapping functions ( Rubenstein, 1990 ).