0000000000567597
AUTHOR
Anne Kölsch
Focal adhesions are hotspots for keratin filament precursor formation
Recent studies showed that keratin filament (KF) formation originates primarily from sites close to the actin-rich cell cortex. To further characterize these sites, we performed multicolor fluorescence imaging of living cells and found drastically increased KF assembly in regions of elevated actin turnover, i.e., in lamellipodia. Abundant KF precursors (KFPs) appeared within these areas at the distal tips of actin stress fibers, moving alongside the stress fibers until their integration into the peripheral KF network. The earliest KFPs were detected next to actin-anchoring focal adhesions (FAs) and were only seen after the establishment of FAs in emerging lamellipodia. Tight spatiotemporal …
Diversification of CYCLOIDEA-like TCP genes in the basal eudicot families Fumariaceae and Papaveraceae s.str.
CYCLOIDEA-like genes belong to the TCP family of transcriptional regulators and have been shown to control different aspects of shoot development in various angiosperm lineages, including flower monosymmetry in asterids and axillary meristem growth in monocots. Genes related to the CYC gene from ANTIRRHINUM show independent duplications in both asterids and rosids. However, it remains unclear to what extent this affected the evolution of flower symmetry and shoot branching in these and other eudicot lineages. Here, we show that CYC-like genes have also undergone duplications in two related Ranunculales families, Fumariaceae and Papaveraceae s.str. These families exhibit morphological divers…
Characterization of the first-in-class T-cell-engaging bispecific single-chain antibody for targeted immunotherapy of solid tumors expressing the oncofetal protein claudin 6.
abstract The fetal tight junction molecule claudin 6 (CLDN6) is virtually absent from any normal tissue, whereas it is aberrantly and frequently expressed in various cancers of high medical need. We engineered 6PHU3, a T-cell-engaging bispecific single chain molecule (bi-(scFv)2) with anti-CD3/anti-CLDN6 specificities, and characterized its pharmacodynamic properties. Our data show that upon engagement by 6PHU3, T cells strongly upregulate cytotoxicity and activation markers, proliferate and acquire an effector phenotype. 6PHU3 exerts potent killing of cancer cells in vitro with EC50 values in the pg/mL range. Subcutaneous xenograft tumors in NSG mice engrafted with human PBMCs are eradicat…
In vivo imaging and quantification of the continuous keratin filament network turnover
Keratin polypeptides are major components of the epithelial cytoskeleton forming a filamentous 3D-network. Like intermediate filament polypeptides of other cell types, keratins make up a stable, but elastic network that is responsible for mechanical stress resilience. At the same time the keratin network is able to change its shape during development, cell division, metastasis and cell migration.