Cofilin-Driven Nuclear Deformation Drives Dendritic Cell Migration through the Extracellular Matrix

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.10.548429v1?rss=1 Authors: Warner, H., Franciosa, G., van der Borg, G., Faas, F., Koenig, C., de Boer, R., Classens, R., Maassen, S., Baranov, M., Mahajan, S., Dabral, D. D., Coenen, B., Bianchi, F., van Hilten, N., Risselada, H. J., Roos, W. H., Olsen, J., Querol Cano, L., van den Bogaart, G. V. Abstract: To mount an adaptive immune response, dendritic cells must process antigens, migrate to lymph nodes and form synapses with T cells. Critical to 3D migration and mechanosensing is the nucleus, which is the size-limiting barrier for navigation through gaps in the extracellular matrix. Here, we show that inflammatory activation of dendritic cells leads to the nucleus becoming spherically deformed, and enables dendritic cells to overcome the typical 2 to 3 micron pore limit for 3D migration. We show that the nuclear shape-change is partially attained through reduced cell adhesion, whereas improved migration through extracellular matrix is achieved through reprogramming of the actin cytoskeleton. Specifically we show that phosphorylation of cofilin-1 at serine 41 drives the assembly of a CofilinActoMyosin (CAM)ring proximal to the nucleus and enhances migration through 3D collagen gels. In summary, these data describe novel signaling events through which dendritic cells simultaneously deform their nucleus and enhance their migratory capacity; molecular events that may be recapitulated in other contexts such as wound healing and cancer. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC