Drawing of a single individual of the rhizopod Gromia terricola from Plate XLVII of Leidy, 1879, showing the extensive network of reticulopodia used in prey capture and transport. This illustration represents one of the major groups of protists discussed in the review by R. A. B. to be found in this issue of cytoskeleton.

Exosomes from wild-type APCs carry vimentin. Exosomes derived from wild-type APCs play an important role in proliferation, migration and ECM production of fibroblasts in vitro. Exosomes derived from wild-type APCs cells promote wound healing in a murine skin excisional injury model.

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ON THE COVER: The front cover image is based on the Original Article Neutrophil-like HL-60 cells expressing only GFP-tagged β-actin exhibit nearly normal motility by Rikki M. Garner et al., https://doi.org/10.1002/cm.21603.

ON THE COVER: The front cover image is based on the Original Article dTACC restricts bouton addition and regulates microtubule organization at the Drosophila neuromuscular junction by David Van Vactor et al., https://doi.org/10.1002/cm.21578.

Cell migration and traction are essential to many biological phenomena, and one of their key features is sensitivity to substrate stiffness, which biophysical models, such as the motor-clutch model and the cell migration simulator can predict and explain. However, these models have not accounted for the finite size of adhesions, the spatial distribution of forces within adhesions. Here, we derive an expression that relates varying adhesion radius ( R) and spatial distribution of force within an adhesion (described by s) to the effective substrate stiffness ( κsub ), as a function of the Young's modulus of the substrate ( E Y ), which yields the relation, , for two-dimensional cell cultures. Experimentally, we found that a cone-shaped force distribution ( s = 1.05) can describe the observed displacements of hydrogels deformed by adherent U251 glioma cells. Also, we found that the experimentally observed adhesion radius increases linearly with the cell protrusion force, consistent with the predictions of the motor-clutch model with spatially distributed clutches. We also found that, theoretically, the influence of one protrusion on another through a continuous elastic environment is negligible. Overall, we conclude cells can potentially control their own interpretation of the mechanics of the environment by controlling adhesion size and spatial distribution of forces within an adhesion.

ON THE COVER: The cover image is based on the Original Article A revised order of subunits in mammalian septin complexes by Ana Paula Araujo et al., https://doi.org/10.1002/cm.21569.

Our previous research has demonstrated that nicotinic acid (NA) might suppress the angiogenesis by modulating the expression of angiogenesis factors and promoting the cytoskeleton remodeling. However, the underlying mechanism need to be further elucidated. The intracellular Ca2+ concentration was measured by a [Ca2+ ] detection kit. The F-actin depolymerization was shown by immunofluorescence staining. The protein levels of F-actin and G-actin were determined by Western blot. The effects of NA treatment on the gelsolin-PI3Kα (p110α) interaction were investigated by co-immunoprecipitation (Co-IP). NA treatment caused an initial drop and then induced a significant increase in [Ca2+ ] with a time and dose dependent manner. In addition, NA promoted the depolymerization of F-actin and knockdown of gelsolin substantially rescued the effects caused by NA treatment. NA treatment significantly inhibited the interaction between phosphoinositide 3-kinase (PI3K) α (p110α) and gelsolin and addition of phosphatidylinositol (3,4,5)-triphosphate (PIP3) increased the protein level of F-actin and rescued the F/G-actin ratio. In conclusion, our results indicated NA treatment could interfere with the ability of PI3Kα (p110α) to inhibit the activity of gelsolin by decomposing PIP2 to produce PIP3, thereby increasing the activity of gelsolin, which ultimately acted on the remodeling of the cytoskeleton and exerted an inhibitory effect on angiogenesis.

Spectrin, the major protein of the erythrocyte membrane skeleton has canonically been thought to only serve a structural function. We have previously described a novel chaperone-like property of spectrin and also hypothesized that the chaperone activity and binding of a hydrophobic ligand, Prodan are localized in the self-association domain. Here we probe the location and molecular origin of the chaperone activity of multi-domain spectrin using a selection of individual recombinant spectrin domains, which we have characterized using intrinsic tryptophan fluorescence and CD spectroscopy to show their identity to native spectrin. Aggregation assays using insulin, ADH, α- and β-globin as well as enzyme refolding assays using alkaline phosphatase and α-glucosidase show that the chaperone activity is not only localized in the self-association domain but is a generalized property of spectrin domains. This is to our understanding, a unique feature in the case of modular multi-repeat proteins, possibly implicating that the large family of "spectrin-repeat" domain containing proteins may also have chaperone like property. Substrate selectivity of chaperone activity as evidenced by the preferential protection of α- over β-globin chains is seen; which has implications in hemoglobin diseases. Moreover, enzyme-refolding assays also indicate alternate modes of chaperone action. We propose that the molecular origin of chaperone activity resides in the surface exposed hydrophobic patches of the spectrin domains as shown by ANS (1-anilinonaphthalene-8-sulfonic acid) and Prodan (6-propionyl-2[dimethylamino]-naphthalene) binding. We also show that Prodan does indeed have a unique binding site on spectrin located at the self-association domain.