Cell Biology

eLife assessment

How misfolded proteins are segregated and cleared is a significant question in mechanistic cell biology, since clearance of these aggregates can protect against pathologies that may otherwise arise. The authors discover a cell cycle stage-dependent clearing mechanism that involves the ER chaperone BiP, the proteosome, and CDK inactivation, but is curiously independent of the APC. These are valuable and interesting new observations, but the evidence supporting these claims is incomplete, and needs to be strengthened and further validated.

eLife assessment

In this important study, Boudjema et al. use cell culture models and advanced microscopic imaging to provide detailed analyses of the cellular events underlying centriole amplification, apical migration, and assembly of hundreds of motile cilia in multi-ciliated cells. This largely descriptive work provides a better understanding of this process that is of interest to cell biologists studying centrioles and cilia. Most of the claims are supported by the data, but the study would benefit from additional analyses regarding the roles of microtubules, which are currently incomplete, and from text editing to improve accessibility and readability, especially for a wider audience.

eLife assessment

This study represents a fundamental contribution to our understanding of how gene expression levels are controlled in bacteria. Through a series of compelling and careful experiments, relying on a mutant that blocks DNA replication but permits growth, and using various methods, the authors reveal how genome concentration rapidly becomes limiting for growth when replication is inhibited. This work contributes to our understanding of the contributions and limiting roles of DNA, mRNA, and ribosomes for growth in bacteria, and will be of considerable interest within both systems biology and microbial physiology.

eLife assessment

The authors explore ER stress signalling mediated by ATF6 using a genome-wide gene depletion screen. They find that the ER chaperone Calreticulin binds and directly represses ATF6; this proposed function for Calreticulin is intriguing and constitutes an important finding. The evidence presented is based on CHO genetic evidence and biochemical results and is convincing.

eLife assessment

The authors present an important study of a multi-cellular platform involving co-culturing of various hiPSC-derived hepatocyte like cells, cholangiocytes, stellate cells and macrophages to mimic the liver microenvironment. The aggregates are then treated with fatty acids and examined through transcriptomic and functional assays. The techniques and methodologically are sound, and the evidence supporting the conclusion is convincing, although more clinically relevant data demonstrating the effect of some potential pharmacological agents on the platform would serve to strengthen the study.

eLife assessment

This important study suggests that capsaicin nanoparticle administration in rats activates the transcription factor Nrf2 by directly binding to its repressor KEAP1, leading to cytoprotective gene induction, and preventing alcohol-induced gastric damage, an avenue to treat alcoholism-related gastric disorders. The evidence is currently incomplete as there is no experimental proof that capsaicin exerts its cytoprotective effects via Nrf2, and not via any of its multiple known pharmacological effects. In particular, Nrf2-deficient mice should be used to show that Nrf2 is causal to the cytoprotective effect, and better controls should be provided for the direct KEAP2-capsaicin interaction, given the high concentrations used.

eLife assessment

This important study builds on a previous publication (with partially overlapping authors), demonstrating that T. brucei has a continuous endomembrane system, which probably facilitates high rates of endocytosis. Using a range of cutting-edge approaches, the authors present compelling evidence that an actomyosin system, with the myosin TbMyo1 as the molecular motor, is localized close to the endosomal system in the bloodstream form (BSF) of Trypanosoma brucei. It shows convincingly that actin plays a role in the organization and integrity of the endosomal system, and that the trypanosome Myo1is an active motor that interacts with actin and transiently associates with endosomes, but a role of Myo1 in endomembrane function in vivo was not directly demonstrated. This work should be of interest to cell biologists and microbiologists working on the cytoskeleton, and unicellular eukaryotes.

eLife assessment

This valuable study contributes to the understanding of phase separation in Dishevelled (DVL) proteins, by investigating the endogenous complexes of DVL2 using ultracentrifugation and contrasting them with DVL1 and DVL3 behavior and the functional validation of the DVL2 intrinsically disordered regions mediating the protein condensate. The study is, however, incomplete due to the lack of several controls and its focus on overexpression and mutants lacking key domains.

eLife assessment

This study provides valuable information on a novel gene that regulates meiotic progression in both male and female meiosis, but the evidence supporting the conclusions of the authors on the role of BEND2 in oogenesis and reproductive aging is incomplete. This study will be of interest to developmental and reproductive biologists.

eLife assessment

This study presents useful findings to inform and improve the in vitro differentiation of hematopoietic progenitor cells from human induced pluripotent stem cells. However, while relying on a well-characterized technical approach, the data analysis is overall incomplete and only partially supports the main conclusions.

eLife assessment

This study uses ex vivo live imaging of the uterus, uterotubal junction, and oviduct post-mating to test the role of the sperm hook in the house mouse (Mus musculus) in sperm movement which could be interesting to evolutionary biologists. The work is useful as their live imaging revealed sperm behaviors in the female tract that have not been previously reported. However, the strength of evidence is incomplete since the limited quantification of the data is insufficient and the extensive speculation on the functions of these sperm behaviors is not supported by sufficient experimental evidence to support their conclusions.

eLife assessment

This important study reports the formation of a new organelle, called giant unilocular vacuole (GUVac), in mammary epithelial cells through a macropinocytosis-like process. The evidence supporting conclusions is solid, using state-of-the-art cell biology techniques. This work will be of interest to cell biologists and contribute to the understanding of cell survival mechanisms against anoikis.

eLife assessment

The manuscript presents a useful model for the field of endosome maturation, providing perspective on the role of the deubiquitinating enzyme UPS-50/USP8 in the process. The evidence presented in the paper is clear, incorporating well-designed experiments that suggest the dual actions of UPS-50 and USP8 in the conversion of early endosomes into late endosomes. Overall, the work is solid and centers on an intriguing subject.

eLife assessment

In this valuable study, Kumar et al., provide evidence suggesting that the p130Cas drives the formation of condensates that sprout from focal adhesions to cytoplasm and suppress translation. Pending further substantiation, this study was found to be likely to provide previously unappreciated insights into the mechanisms linking focal adhesions to the regulation of protein synthesis and was thus considered to be of broad general interest. However, the evidence supporting the proposed model was incomplete; additional evidence is warranted to substantiate the relationship between p130Cas condensates and mRNA translation and establish corresponding functional consequences.

eLife assessment

This study reports useful data suggesting the critical roles of two ancient proteins, XAP5 and XAP5L, in controlling the transcriptional program of ciliogenesis during mouse spermatogenesis. However, this study is considered incomplete because the data only partially support the conclusion. This work will be of interest to biomedical researchers who work on ciliogenesis and reproduction.

eLife assessment

This paper presents a valuable automated method to track individual mammalian cells as they progress through the cell cycle using the FUCCI system. The authors have developed a technique for analyzing cells that grow in suspension and used their method to look at different tumor cell lines that grow in suspension and determine the effect of drugs that directly affect the cell cycle. They show solid evidence that the method can be applied to both adherent and non-adherent cell lines. This paper will be of interest to cell biologists investigating cell cycle effects.

eLife assessment

This valuable study delineates the cellular contributions of BMP signaling in liver development and function. The findings are convincing, and the study employs state-of-the-art molecular, genetic, and cellular approaches to demonstrate that hepatic stellate cells play a central role in liver health by mediating cell-to-cell crosstalk via the production of specific BMP proteins. This study will be of interest to scientists interested in developmental biology and organ physiology.

eLife assessment

This study is focused on the question of how Nrp1 contributes to the regulation of vascular permeability and whether or why there are differences between different vascular beds. The scientific concept of this paper suggests a possible role of Nrp1 on perivascular cells as a participant in the regulation of vascular permeability. This concept is interesting and potentially useful. However, the methodology and quantitative analysis are currently inadequate to fully support the claims.

eLife assessment

This valuable study demonstrates how proximity labeling with streptavidin can be used to boost fluorescence signals in otherwise hard-to-label regions of cells. The technique can outperform the immunofluorescence of epitope tags in phase-separated regions, but the experimental verification is incomplete and would benefit from additional controls. This study will be of particular interest to those using correlative light and electron microscopy or expansion microscopy when the signal is limiting or inaccessible.

eLife assessment

The authors present evidence that small extracellular vesicles can be secreted from cells inside larger vesicles that they call amphiectosomes, which then tear to release their small vesicle contents. There are questions and concerns relating to the quality of the data and the in vivo significance of the observations. The findings are potentially important but the data are incomplete and the claims are only partially supported.