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localized microdomains. Because the rate of actin polymerization is directly
proportional to the amount of free G-actin (
Pollard and Borisy, 2003
),
the local synthesis of actin confined to the leading edge of a cell may be
one mechanism by which actin polymerization is increased to promote cell
migration. Additionally, local synthesis of actin may promote
de novo
actin
filament nucleation. The cytosolic chaperone protein (CCT) is required
for proper actin folding following translation, and has been shown to
associate with F-actin, possibly acting as a nucleation factor itself to pro-
mote
de novo
filament formation from newly translated actin monomers
(
Grantham et al., 2002
;
Pappenberger et al., 2006
). Lastly, newly synthesized
actin may be more readily polymerized than preexisting actin monomers.
Posttranslational modifications of preexisting actin could negatively affect
polymerization, which has been demonstrated in at least one case with
the glutathionylation of actin (
Wang et al., 2001
). Although it is unclear to
what extent the population of pre-existing actin is glutathionylated, it is
plausible that locally synthesized actin monomers may be rapidly integrated
into filaments before glutathionylation could occur, providing an additional
mechanism to promote localized actin dynamics.
4.3. Posttranslational Regulation of Actin Isoforms
In addition to glutathionylation, actin can also be acetylated (
Rubenstein
and Martin, 1983
), arginylated (
Karakozova et al., 2006
), phosphorylated
(
Gu et al., 2003
;
Vandermoere et al., 2007
), ubiquitinated (
Burgess et al.,
2004
;
Kudryashova et al., 2005
), and SUMOylated (
Hofmann et al., 2009
).
However, while the acetylation of muscle actins differs slightly from the
cytoplasmic actins (
Rubenstein, 1990
), no differential posttranslational
modifications of cytoplasmic actins have been identified with one intrigu-
ing exception. β-actin was reported to be specifically arginylated at its
N-terminus (
Karakozova et al., 2006
), creating a bulky positive charge
thought to be critical for promoting the branched actin networks found
in lamellipodia. Indeed, fibroblasts deficient for the enzyme responsible for
the arginylation of β-actin, arginyltransferase-1 (
Ate1
), exhibited abnormal
morphology and impaired migration that could be rescued by a genetically
encoded and permanently arginylated β-actin (
Karakozova et al., 2006
).
Ate1
was subsequently found to arginylate a large number of other proteins
including additional sites on β-actin as well as α-cardiac-actin and a num-
ber of actin-binding proteins (
Wong et al., 2007
). Interestingly, arginylated
γ-actin was not detected in these initial experiments. Subsequent work by
this group reported that γ-actin was also arginylated, but that differences in
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