Centrosomes are the main microtubule-organizing centres in most animal cells. A recent study demonstrates that these organelles also nucleate actin filaments.
The centrosome comprises a pair of centrioles, surrounded by proteinaceous pericentriolar material (PCM), which is the main site of microtubule nucleation. Additionally, centrosomes contain granules known as centriolar satellites, which are transported from the cytoplasm by dynein. The presence of actin and actin-associated proteins on isolated centrosomes has also been reported but was considered to be cytoplasm contamination. In their recent study, Farina et al. set out to investigate a potential direct link between the centrosome and the actin cytoskeleton and showed that, in fact, actin filaments actively assemble on centrosomes.
“Actin was assembled through the elongation of pre-existing filaments, as well as by de novo nucleation”
The authors first demonstrated that isolated centrosomes can robustly generate large radial arrays of actin filaments. Actin was assembled through the elongation of pre-existing filaments, as well as by de novo nucleation. Importantly, in fixed cultured cells, centrosomes were found surrounded by a cloud of actin filaments, indicating that actin is assembled on centrosomes in the cellular context as well.
In order to study the mechanism of centrosome-mediated actin assembly, the authors next aimed to delineate factors involved in this process. It was revealed that both in vitro and in cells, centrosomes are associated with the actin-related protein 2/3 (Arp2/3) complex, which is a known actin nucleator. It was further demonstrated that this complex is an important mediator of actin assembly at the centrosome, and that this process is regulated by the nucleation-promoting factor Wiskott–Aldrich syndrome protein and scar homologue (WASH).
To understand how actin assembly factors interact with centrosomal components, the authors analysed the composition of actin filament-containing structures obtained during centrosome purification. This analysis provided evidence that centrioles serve as the main scaffold for actin nucleation, as the majority of actin asters were found associated with acetylated tubulin (the main structural constituent of centrioles). Additionally, actin asters associated with the major component of centriolar satellites, PCM1. Knockdown of PCM1 perturbed Arp2/3 complex and WASH localization, as well as actin assembly, at the centrosome in cultured cells. The centrosomal localization of Arp2/3 complex and WASH was also impaired by the perturbation of dynein-based transport. This collectively indicates the importance of centrioles, as well as centriolar satellites and their transportation by dynein in the recruitment and anchoring of actin assembly factors to the centrosome.
In sum, Farina et al. reveal a previously unanticipated role of the centrosome as an actin-organizing centre. It would be interesting to establish the physiological importance of this novel centrosome function and study how microtubule and actin assembly are spatially and functionally co-regulated.
Farina, F. et al. The centrosome is an actin-organizing centre. Nat. Cell Biol. http://dx.doi.org/10.1038/ncb3285 (2015)