Absence of the Drosophila Jump Muscle Actin Act79B is
Compensated by Up-regulation of Act88F
Tracy E. Dohn and Richard M. Cripps *
Department of Biology, University of New Mexico, Albuquerque, New Mexico
Background: Actins are structural components of the cytoskeleton and muscle, and numerous actin isoforms are found in
most organisms. However, many actin isoforms are expressed in distinct patterns allowing each actin to have a specialized
function. Numerous studies have demonstrated that actin isoforms both can and cannot compensate for each other under
speciﬁc circumstances. This allows for an ambiguity of whether isoforms are functionally distinct.
Results: In this study, we
analyzed mutants of Drosophila Act79B, the predominant actin expressed in the adult jump muscle. Functional and structural
analysis of the Act79B mutants found the ﬂies to have normal jumping ability and sarcomere structure. Analysis of actin gene
expression determined that expression of Act88F, an actin gene normally expressed in the ﬂight muscles, was signiﬁcantly up-
regulated in the jump muscles of mutants. This indicated that loss of Act79B caused expansion of Act88F expression. When
we created double mutants of Act79B and Act88F, this abolished the jump ability of the ﬂies and resulted in severe defects in
Conclusions: These results indicate that Act88F can functionally substitute for Act79B in the jump muscle,
and that the functional compensation in actin expression in the jump muscles only occurs through Act88F. Developmental
Dynamics 247:642–649, 2018.
2018 Wiley Periodicals, Inc.
Key words: Actin; Drosophila; muscle; actin isoform; paralogous compensation
Submitted 1 December 2017; First Decision 4 January 2018; Accepted 8 January 2018; Published online 10 January 2018
The actin isoforms found in invertebrates and mammals are
highly conserved between species illustrating their key roles in
development and cell function (Perrin and Ervasti, 2010). Actins
are found ubiquitously in the cytosol of eukaryotic cells where
they have essential roles in cell shape, motility, and even tran-
scriptional regulation (Dominguez and Holmes, 2011). Muscle
actins form the core component of the thin ﬁlaments of the sar-
comere, which is the basic contractile unit in muscle cells. Most
organisms have multiple actin genes encoding highly conserved
actin isoforms (Perrin and Ervasti, 2010). However, these isoforms
are often segregated by expression pattern and developmental
timing giving speciﬁc, nonoverlapping functions for the actin
oper et al., 2005). For example some actins are found
solely in the cytosol, while others are speciﬁc to muscle sarco-
meres (Mohun et al., 1984; Fyrberg et al., 1998; Perrin and
Ervasti, 2010; Kijima et al., 2015).
A study looking at the role of actin isoforms in multiple struc-
tures used overexpression constructs to demonstrate that multiple
actin isoforms are capable of integrating with existing isoforms
in cytosolic actin processes, such as the formation of lamellipodia
and ﬁlopodia and within the sarcomere of each muscle subtype
oper et al., 2005). Nevertheless, functional and biochemical
assays have also demonstrated that actin isoforms can have dis-
tinct properties which do not allow complete compensation
between different actins (Fyrberg et al., 1998; Perrin and Ervasti,
2010; Kijima et al., 2015). Most notably the actin–myosin inter-
action in the muscle sarcomere is very sensitive to both the actin
and myosin isoform present such that isoform exchange can lead
to differential actin–myosin binding afﬁnity (Lowey et al., 2013;
Kijima et al., 2015; Miller et al., 2015; Nikitina et al., 2016).
Unique roles of the actin isoforms are also observed in nemaline
myopathies, in which loss of a single actin isoform leads to a
spectrum of disorders, from severe disease requiring intervention
at birth to a mild disease that allows viability into adulthood
(Ilkovski et al., 2001).
Animal models deﬁcient for speciﬁc actin isoforms have shown
expanded expression domains of other isoforms, indicating a
potential for compensation among different actins. In alpha-
cardiac-actin deﬁcient mice, vascular smooth muscle and skeletal
actins increased expression in the heart (Kumar et al., 1997).
Likewise, alpha-cardiac-actin and vascular speciﬁc actins were
increased in alpha-skeletal-actin deﬁcient mice and human
nemaline myopathy patients (Crawford et al., 2002; Nowak et al.,
2007, 2009). However, this compensatory up-regulation of alter-
native actin isoforms does not restore muscle function and does
Grant sponsor: NIH; Grant number: R01 GM061738; Grant sponsor:
ASERT/IRACDA; Grant number: K12 GM088021; Grant sponsor:
the Institute Development Award (IDeA) Program of NIGMS; Grant
number: P20 GM103452.
*Correspondence to: Richard M. Cripps, Department of Biology, University
of New Mexico, Albuquerque, NM 87131. E-mail: email@example.com
Article is online at: http://onlinelibrary.wiley.com/doi/10.1002/dvdy.
2018 Wiley Periodicals, Inc.
DEVELOPMENTAL DYNAMICS 247:642–649, 2018