Distinct developmental functions for cytoplasmic actin isoforms.

Abstract

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.