Summary
Nuclear actin polymerization is observed in an increasing number of biological processes including DNA replication stress [1-6] and T cell receptor (TCR) signaling in CD4 T cells [7]. TCR activation induces the formation of F-actin in the cytoplasm and the nucleus to strengthen contacts to antigen presenting cells and drive a gene expression program to shape humoral immune responses, respectively [7-11]. Interestingly, these two actin remodeling events are phenotypically different and appear to be mechanistically uncoupled from each other but both involve actin polymerization by the Arp2/3 complex. The Arp2/3-complex consists of 7 subunits where ARP3, ARPC1 and ARPC5 exist as two different isoforms in humans that can assemble in complexes with different properties [12-17]. Here we examined whether specific Arp2/3 subunit isoforms are responsible for distinct actin remodeling events in CD4 T cells. Transient silencing or knock out of individual subunit isoforms demonstrates that in response to TCR signaling, the ARPC5L isoform is involved in nuclear actin polymerization, while cytoplasmic actin dynamics selectively relies on ARPC5. In contrast, nuclear actin polymerization triggered by DNA replication stress in CD4 T cells required ARPC5 and was independent of ARPC5L. Moreover, nuclear Ca2+ transients, which are essential for TCR-induced nuclear actin polymerization, were dispensable for nuclear actin filament formation during DNA replication stress. Our results reveal that the selective involvement of ARPC5 isoforms governs the activity of Arp2/3 complex in distinct actin polymerization events and imply nuclear Ca2+ transients as selective trigger for ARPC5L-dependent nuclear actin polymerization.
Competing Interest Statement
The authors have declared no competing interest.