Actins are among the most highly expressed proteins in eukaryotes and play a
critical role in most cellular processes. In mammals there exists six different actin
isoforms, of which only the cytoplasmic βcyto- and γcyto-actins are ubiquitously expressed.
Remarkably, the cytoplasmic actins differ at only 4 out of 375 amino acids and have been
exactly conserved from birds to mammals. It has been postulated that βcyto- and γcytoactin
have distinct biological functions; therefore, to test this hypothesis we generated null alleles of the Actb and Actg1 genes. Characterization of the resulting isoformspecific
null animals demonstrates that βcyto-actin but not γcyto-actin is essential for
embryonic viability. While γcyto-actin is largely dispensable for embryonic development,
it does confer growth and survival advantages, as evidenced by the fact that γcyto-actin
null embryos exhibited mild developmental delays and decreased postnatal survival Furthermore, γcyto-actin null primary mouse embryonic fibroblasts (MEFs) had a mild
growth deficiency and a slight increase in apoptosis, despite total actin levels being
maintained. In contrast to γcyto-actin null mice, βcyto-actin null mice were early
embryonic lethal, indicating that βcyto-actin is an essential gene required for
embryogenesis. The lethality in βcyto-actin null mice is likely due to defects in cell
growth and migration as these processes were severely impaired in βcyto-actin knockout
primary MEFs. Together, the distinct phenotypes observed in βcyto- and γcyto-actin
knockout mice and cells demonstrate that while βcyto- and γcyto-actin can compensate for
each other to a limited extent, they also have unique biological functions.
University of Minnesota Ph.D. dissertation. December 2010. Major: Biochemistry, Molecular Bio, and Biophysics. Advisor: James M. Ervasti. 1 computer file (PDF); ix, 128 pages. Includes appendix. Ill. (some col.)
Bunnell, Tina M..
Distinct developmental functions for cytoplasmic actin isoforms..
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