3d) or in mouse ear explants (Supplementary Movie 6), and also in myeloid cells migrating in live Medaka fish, showed that the degree of nuclear deformation correlated with an accumulation of actin around the nucleus (Fig. This suggests that a specific set of actin filaments is assembled around the nucleus of a DC when it is strongly confined in vitro and in vivo.We propose to name this network confinement induced actin network (Ci AN).(a) Sequential images of a representative Life Act-GFP (green) expressing DC stained with Hoechst (red) passing a 2-μm-wide constriction. (b) Normalized mean actin intensity around the nucleus (green) and nuclear circularity (red) of cells crossing 2-μm-wide constrictions as a function of the nuclear centre of mass position relative to the centre of the constriction.This Arp2/3-nucleated perinuclear actin network allows nuclear deformation and the subsequent cell passage through constrictions, probably by rupturing the intranuclear lamina shell. 1A, B) or cultured cells used as model systems for tumour invasion (fibrosarcoma cells HT1080 and breast adenocarcinoma MDA-MB231; Supplementary Fig.
Imaging of actin filaments in DCs migrating in dense, 3 mg m L (Fig.
Immune cells such as neutrophils do not express lamin A/C and have a short lifespan (dying at the site of infection); however, dendritic cells (DCs), which patrol peripheral tissues and present antigens to T cells in lymph nodes, need to combine a high migration capacity and long-term survival, a combination which might also be essential for the metastatic capability of some cancer cells the nucleus limits confined 3D migration in DCs.
We show that DCs overcome this physical limitation by generating a dense and dynamic perinuclear actin network nucleated by Arp2/3 downstream of Wave2. However, they have a lower expression level of lamin A/C proteins than mouse embryonic fibroblasts (Supplementary Fig.
This well-defined set of physico-chemical processes, initially described based on cultured cells moving on flat glass surfaces, seems to be universal among migrating cells.
Nevertheless, recent studies performed in more complex environments have proposed alternative scenarios and additional requirements for cell locomotion, suggesting that the precise function of some proteins might depend on the environment of migrating cells.