Highlights d Phosphoproteomics analysis of SARS-CoV-2-infected cells uncovers signaling rewiring d Infection promotes host p38 MAPK cascade activity and shutdown of mitotic kinases d Infection stimulates CK2-containing filopodial protrusions with budding virus d Kinase activity analysis identifies potent antiviral drugs and compounds

Summary Cytoskeletal cross talk between actin filaments and microtubules is a common mechanism governing the assembly of cellular structures, i.e., during filopodia formation or cilia organization. However, potential actin-microtubule interactions during mammalian cell divisions are less well understood. At mitotic entry, centrosomes propagate the formation of the mitotic spindle, thereby aligning individual chromosomes to the metaphase plate, a process coined chromosome congression . Here, we identify actin filament assembly spatially defined at centrosomes contemporaneously with spindle microtubules forming during prometaphase. We show that pharmacological Arp2/3 complex inhibition as well as overexpression of the Arp2/3 complex inhibitory protein Arpin decreased spindle actin. As a consequence, mitotic spindle formation is impaired, which resulted in disorganized chromosome congression and ultimately mitotic defects in non-transformed cells. Thus centrosomal Arp2/3 complex activity plays a role in the maintenance of genomic integrity during mitosis.

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Formin-mediated bridging of cell wall, plasma membrane, and cytoskeleton in symbiotic infections of Medicago truncatula Graphical abstract Highlights d The SYMBIOTIC FORMIN 1 (SYFO1) specifically regulates symbiotic root hair curling d SYFO1 directly binds actin and polarizes in responding root hairs d SYFO1 induces membrane protrusions in cell-wall-devoid protoplasts d Cell wall association of SYFO1 is indispensable for its function in root hairs

Steroid hormone receptors are ligand-binding transcription factors essential for mammalian physiology. The androgen receptor (AR) binds androgens mediating gene expression for sexual, somatic, and behavioral functions, and is involved in various conditions including androgen-insensitivity-syndrome (AIS) or prostate cancer. Here we identified functional AIS-patient mutations in the formin and actin nucleator DAAM2. DAAM2 localized to the nucleus and colocalized with the AR to form actin-dependent transcriptional droplets in response to dihydrotestosterone. DAAM2-AR-droplets ranged from 0.02 to 0.06 µm3 in size and associated with active RNA polymerase II. DAAM2 polymerizes actin directly at the AR to promote droplet fusion in a highly dynamic manner and actin polymerization is required for prostate-specific antigen expression in cancer cells. Our data uncover signal-regulated nuclear actin assembly at a steroid hormone receptor necessary for transcription.