Biology subjects

Windhorst, S.

Publications and source records attributed to Windhorst, S..

3 recordsLinked to original sources

bioRxiv2025

Discovery of a new evolutionarily conserved short linear F-actin binding motif

Regulation of the actin cytoskeleton by actin binding proteins (ABPs) is essential for cellular homeostasis, and the mode of actin binding determines the activity of ABPs. Here, we discovered a novel "Short linear F-actin binding motif (SFM)" on the basis of the cryo-EM structure of the ITPKA-F-actin complex. We developed the computational pipeline SLiMFold, which identified 103 human SFM containing-proteins exhibiting diverse cellular functions. The SFM probably developed ex nihilo and remained conserved in eukaryotes, with a binding affinity to F-actin ranging from 13 to 89 {micro}M. Furthermore, we uncovered the essential amino acids of this SFM for F-actin binding and affinity modulation. Together, the SFM seems to serve as a low affinity anchor to target proteins to F-actin, in order to connect the regulation of actin dynamics with broad cellular functions. These findings will shed new light on the role of a wide variety of proteins.

biochemistry↗

bioRxiv2024

Red blood cell-tumour cell interactions promote tumour cell progression

One critical step in the metastatic cascade is the survival of circulating tumour cells (CTCs) within the bloodstream. While numerous interactions between CTCs and various hematopoietic cells have been described, the role of red blood cells (RBCs) in this process remains underexplored. This study investigates the interactions between tumour cells and RBCs from breast and lung cancer patients, revealing significant phenotypic and functional changes in the tumour cells, unlike when the contact is with RBCs from healthy donors. In vitro co-culture of cancer cell lines with RBCs from metastatic cancer patients resulted in increased tumour cell attachment accompanied by morphological changes. Additionally, RBCs-primed tumour cells showed increased adhesion and disruption of the endothelial barrier in vitro and increased invasiveness both in vitro and in vivo. Transcriptomic analysis showed that RBCs from metastatic breast cancer patients induce significant gene expression changes, notably upregulating PAK4, which enhances migration and epithelial-mesenchymal transition. PAK4 inhibition reduced these effects. Proteomic studies revealed substantial remodelling, including actin-related changes and the accumulation of VASP at cell edges, promoting directional migration. Clinically, higher RBC distribution width (RDW) in metastatic breast cancer patients is associated with increased CTC counts and worse outcome. This study highlights the previously unrecognized role of RBCs in promoting metastatic behaviours in cancer cells and suggests potential therapeutic targets, such as PAK4, to counteract these effects. Further exploration of RBCs-tumour cell interactions could provide new insights into metastatic mechanisms and improve cancer prognosis and treatment strategies. Key PointsO_LIThis study reveals the previously unknown role of RBCs in enhancing tumour cell invasiveness and metastatic potential. C_LIO_LITumour cells undergo significant phenotypic and functional changes after contact with RBCs from cancer patients. C_LI

cancer biology↗

bioRxiv2018

Radial F-actin Organization During Early Neuronal Development

The centrosome is thought to be the major neuronal microtubule-organizing center (MTOC) in early neuronal development, producing microtubules with a radial organization. In addition, albeit in vitro, recent work showed that isolated centrosomes could serve as an actin-organizing center (Farina et al., 2016), raising the possibility that neuronal development may, in addition, require a centrosome-based actin radial organization. Here we report, using super-resolution microscopy and live-cell imaging, F-actin organization around the centrosome with dynamic F-actin aster-like structures with F-actin fibers extending and retracting actively. Photoconversion/photoactivation experiments and molecular manipulations of F-actin stability reveal a robust flux of somatic F-actin towards the cell periphery. Finally, we show that somatic F-actin intermingles with centrosomal PCM-1 satellites. Knockdown of PCM-1 and disruption of centrosomal activity not only affect F-actin dynamics near the centrosome but also in distal growth cones. Collectively the data show a radial F-actin organization during early neuronal development, which might be a cellular mechanism for providing peripheral regions with a fast and continuous source of actin polymers; hence sustaining initial neuronal development.

neuroscience↗