It was known that actin cytoskeleton-related proteins are involved in other examples of symmetry, in particular, the myosin 1d and 1c which is needed for asymmetric hindgut and male genitalia development in Drosophila, and myosin 1d is sufficient to cause chirality in other Drosophila organs. However, it remains to be discovered whether left-right asymmetry occurs as a result of the activity of a single chiral determinant such as myosin 1d or mediated through the coordinated activities of a group of proteins.
This article shows that knockdown of diaphanous-related formin, mDia1, did not prevent the formation of either radial or transverse fibres, but abolished the tilting of the radial fibres (Fig. 1f). Hence mDia1 depleted cells exhibited a radially symmetric organisation of the actin cytoskeleton. Other formins such as FMNL2, FHOD3, Daam1 knockdowns reduced the degree of actin cytoskeleton chirality, albeit not to such an extent as knockdown of mDia1. The effect of knockdowns of other major regulators of actin polymerisation was also studied. Results showed that suppressing actin-nucleating Arp2/3 complex via the knockdown of its major component ARPC2 resulted in inhibition of actin cytoskeleton chirality (Fig. 5a and 5b).
Figure 1. Quantification of radial fibre tilt reveals a decrease in actin cytoskeleton chirality in mDia1 knockdown cells.
Figure 5. Formin mDia1 is dispensable for the development of clockwise actin cytoskeleton chirality in profilin 1 knockdown.
The siRNA-mediated knockdown of profilin-1 (actin monomer sequestering proteins), reversed the direction of actin swirling in cells, resulting in sinistral chirality pattern. Also, depletion of 90% of profilin-2 did not reverse the chirality direction but, increased the anti-clockwise chirality in terms of radial fibre tilt.
Thus, actin-driven chirality may underlie tissue and organ asymmetry.
The full article can be accessed here.
