Essential nucleotide- and protein-dependent functions ofActb/β-actin

Abstract

The highly similar cytoplasmic β- and γ-actins differ by only four functionally similar amino acids, yet previous in vitro and in vivo data suggest that they support unique functions due to striking phenotypic differences between and null mouse and cell models. To determine whether the four amino acid variances were responsible for the functional differences between cytoplasmic actins, we gene edited the endogenous mouse locus to translate γ-actin protein. The resulting mice and primary embryonic fibroblasts completely lacked β-actin protein, but were viable and did not present with the most overt and severe cell and organismal phenotypes observed with gene knockout. Nonetheless, the edited mice exhibited progressive high-frequency hearing loss and degeneration of actin-based stereocilia as previously reported for hair cell-specific knockout mice. Thus, β-actin protein is not required for general cellular functions, but is necessary to maintain auditory stereocilia.

Modular actin nano-architecture enables podosome protrusion and mechanosensing

“…While the cPM primarily consists of β-actin, the pPM is mostly built up from γ-actin. Understanding the non-redundant function of actin isoforms in cytoskeletal remodeling is an area of steeply emerging interest (46)(47)(48). Although not much is known about the different functions of the two isoforms, it is generally assumed that β-actin is preferentially located to protrusive lamellipodial structures and γ-actin to stress fibers (31), something which we also observed in DCs.…”

Single-cell proteomics reveals changes in expression during hair-cell development

“…Nevertheless, Actb or Actg1 knockout mice have normal stereocilia development, suggesting that the two isoforms are interchangeable in mice, at least initially (Belyantseva et al, 2009; Perrin et al, 2010). Phenotypes of aging hair cells from the two mutants differ, however, and these differences arise from the ACTB and ACTG1 proteins themselves, not expression dynamics (Perrin et al, 2010; Patrinostro et al, 2018).…”

Transcriptional and cytopathological hallmarks of FSHD in chronic DUX4-expressing mice

“…EDL muscles were anchored to a force transducer and incubated in Krebs-Ringer bicarbonate buffer. Baseline contractile force measurements and passive stiffness were conducted as previously described (41,42). For eccentric contractions, EDL muscles were passively shortened to 90% resting length and then maximally stimulated for 200 ms while the muscle was simultaneously lengthened to 110% resting length at 0.5 lengths/s.…”