Actin Isoforms in Neuronal Development and Function - International Review of Cell and Molecular Biology - page 167

reported stronger binding of a number of proteins including cofilin ( De La
Cruz, 2005 ), β-cap73 ( Shuster et al., 1996 ), ezrin ( Yao et al., 1996 ), L-plastin
( Namba et al., 1992 ), and profilin ( Larsson and Lindberg, 1988 ) to prepa-
rations rich in β-actin compared to muscle actin enriched samples. While
intriguing, in terms of actin isoforms, this is analogous to comparing apples
to oranges, and it is difficult to reconcile the significance of these findings
as it pertains to differential binding of the nearly identical cytoplasmic actin
isoforms.
5. ROLES FOR ACTIN ISOFORMS IN NEURONAL
DEVELOPMENT AND FUNCTION
In the preceding sections, we introduced the actin isoforms and what
is currently known regarding their biochemical characteristics and regula-
tory mechanisms. Much of this work is relatively indirect and mostly con-
ducted with purified biochemical preparations or in nonneuronal cell types.
We will review what has been learned regarding actin isoform functions in
neurons from in vitro and cell culture-based studies. This encompasses the
bulk of what is currently known regarding the roles of actin isoforms in
neuronal development and function. These studies will then be compared
to what has been learned from recently developed in vivo animal models.
5.1. Actin Isoform Expression Patterns during Neuronal
Differentiation and Brain Development
5.1.1. Temporal and Protein Level Regulation
As described in the introductory sections, no endogenous α-actin isoforms
have been detected in neuronal preparations, leaving only the cytoplasmic
β- and γ-actins to fulfill the functions of the actin cytoskeleton in neu-
rons. Some of the first attempts at elucidating the functions of the cytoplas-
mic actins in neurons assessed their expression levels and localization. Early
work in PC12 neuron-like cell lines demonstrated that nerve growth factor
(NGF)-induced differentiation and neurite extension resulted in a rapid
increase in the expression of both β- and γ-actin mRNA, followed by a
more gradual reduction in levels such that both mRNAs returned to pre-
treatment levels by 15 days post-NGF introduction ( Henke et al., 1991 ).
At the protein level, however, β- and γ-actin were both elevated following
NGF treatment and most intriguingly, the relative composition of actin
within these cells appeared to change such that γ-actin made up a sig-
nificantly larger proportion of the total actin population at the end of the