Cell Biology

Arpin deficiency increases actomyosin contractility and vascular permeability

1. Armando Montoya-Garcia
2. Idaira M Guerrero-Fonseca
3. Sandra D Chanez-Paredes
4. Karina B Hernandez-Almaraz
5. Iliana I Leon-Vega
6. Angelica Silva-Olivares
7. Abigail Betanzos
8. Monica Mondragon-Castelan
9. Ricardo Mondragon-Flores
10. Citlaltepetl Salinas-Lara
11. Hilda Vargas-Robles
12. Michael Schnoor

• Curated by eLife

  eLife assessment

  This study presents solid results to demonstrate that arpin is expressed in the endothelium of blood vessels and that its deficiency leads to leaky blood vessels in in vivo and in vitro models. The work does not yet clarify the mechanistic connection between arpin and increased ROCK activity. The study adds some insights to our understanding of the complicated network of proteins that control this process, and it will be useful to individuals within this defined field of study.

Reviewed by eLife

Human rod photoreceptor outer segments are supported by accessory inner segment structures

1. Tylor R. Lewis
2. Natalia V. Klementieva
3. Sebastien Phan
4. Carson M. Castillo
5. Keun-Young Kim
6. Lauren Y. Cao
7. Mark H. Ellisman
8. Vadim Y. Arshavsky
9. Oleg Alekseev

Reviewed by Arcadia Science

Topological stress triggers persistent DNA lesions in ribosomal DNA with ensuing formation of PML-nucleolar compartment

1. Alexandra Urbancokova
2. Terezie Hornofova
3. Josef Novak
4. Sarka Andrs Salajkova
5. Sona Stemberkova Hubackova
6. Alena Uvizl
7. Tereza Buchtova
8. Martin Mistrik
9. Brian McStay
10. Zdenek Hodny
11. Jiri Bartek
12. Pavla Vasicova

• Curated by eLife

  eLife assessment

  This valuable study asks how Promyelocytic leukemia protein (PML) becomes associated with the nucleoli of cells (PML Nucleolar Associations, PNAs) upon various genotoxic stimuli. Using immunostaining analysis with induced DNA double-strand breaks (DSBs) in rDNA repeats, the authors provide solid evidence that PNAs are triggered mostly by the inhibition of topoisomerase and RNA polymerase I, which is augmented by homologous recombination but not by the non-homologous end joining double-strand break repair pathway. The findings have potential implications for a better understanding of how DNA damage in ribosomal DNA is repaired for genome stability. This paper is of interest to researchers in the fields of nuclear structure and DNA repair.

Reviewed by eLife

SARS-CoV-2 NSP13 interacts with TEAD to suppress Hippo-YAP signaling

1. Fansen Meng
2. Jong Hwan Kim
3. Chang-Ru Tsai
4. Jeffrey D Steimle
5. Jun Wang
6. Yufeng Shi
7. Rich G Li
8. Bing Xie
9. Vaibhav Deshmukh
10. Shijie Liu
11. Xiao Li
12. James F Martin

• Curated by eLife

  eLife assessment

  This important study reports the molecular function of the SARS-CoV-2 helicase NSP13, which inhibits the transcriptional activity of the YAP/TEAD complex in vitro and in vivo. The evidence supporting the authors' claims is solid, with rigorous cell biological assays and multi-omic studies. This work will be of interest to scientists studying COVID-19 infection and the Hippo-YAP signaling pathway.

Reviewed by eLife

AARS2 ameliorates myocardial ischemia via fine-tuning PKM2-mediated metabolism

1. Zongwang Zhang
2. Lixia Zheng
3. Yang Chen
4. Yuanyuan Chen
5. Junjie Hou
6. Chenglu Xiao
7. Xiaojun Zhu
8. Shi-Min Zhao
9. Jing-Wei Xiong

• Curated by eLife

  eLife assessment

  This valuable study demonstrates that AARS2 is crucial for protecting cardiomyocytes from ischemic stress by shifting energy metabolism towards glycolysis through PKM2, presenting a novel therapeutic target for myocardial infarction. The findings are supported by solid evidence, including cardiomyocyte-specific genetic modifications, functional assays, and ribosome profiling, which together robustly validate the AARS2-PKM2 signaling pathway's role in cardiac protection.

Reviewed by eLife

Allosteric modulation of the CXCR4:CXCL12 axis by targeting receptor nanoclustering via the TMV-TMVI domain

1. Eva M García-Cuesta
2. Pablo Martínez
3. Karthik Selvaraju
4. Gabriel Ulltjärn
5. Adrián Miguel Gómez Pozo
6. Gianluca D'Agostino
7. Sofia Gardeta
8. Adriana Quijada-Freire
9. Patricia Blanco Gabella
10. Carlos Roca
11. Daniel del Hoyo
12. Rodrigo Jiménez-Saiz
13. Alfonso García-Rubia
14. Blanca Soler Palacios
15. Pilar Lucas
16. Rosa Ayala-Bueno
17. Noelia Santander Acerete
18. Yolanda Carrasco
19. Carlos Oscar Sorzano
20. Ana Martinez
21. Nuria E Campillo
22. Lasse D Jensen
23. Jose Miguel Rodriguez Frade
24. César Santiago
25. Mario Mellado

• Curated by eLife

  eLife assessment

  This is an important study that describes an elegant modelling driven approach to design of allosteric antagonists for CXCR4 that have a selective effect on receptor nanocluster formation, cell polarisation and chemotaxis, but spare binding of CXCL12 to the receptor and inhibition of adenylate cyclase. This enables selective targeting of processes dependent upon cell polarisation and chemotaxis without impacting signalling effects and may avoid some of the toxicity associated with antagonists that target CXCL12 binding and thus block all CXCR4 signalling. The revised manuscript offers convincing evidence to support the claims. The modelling work is better described and additional data has been presented that better illustrates the unique features of the new antagonist. The in vivo studies in the zebrafish model open a path to studies in mammalian models.

Reviewed by eLife

The actomyosin system is essential for the integrity of the endosomal system in bloodstream form Trypanosoma brucei

1. Fabian Link
2. Sisco Jung
3. Xenia Malzer
4. Felix Zierhut
5. Antonia Konle
6. Alyssa Borges
7. Christopher Batters
8. Monika Weiland
9. Mara Pöllmann
10. An Binh Nguyen
11. Johannes Kullmann
12. Claudia Veigel
13. Markus Engstler
14. Brooke Morriswood

• Curated by eLife

  eLife assessment

  This important study builds on a previous publication, 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 an active molecular motor, is localized close to and can associate with the endosomal system in the bloodstream form of Trypanosoma brucei. It shows convincingly that both actin and Myo I play a role in the organization and integrity of the endosomal system: both RNAi-mediated depletion of Myo1, and treatment of the cells with latrunculin A resulted in endomembrane disruption. This work should be of interest to cell biologists and microbiologists working on the cytoskeleton, and unicellular eukaryotes.

Reviewed by eLife, Arcadia Science

Endosomal Chemokine Receptor Signalosomes Regulate Central Mechanisms Underlying Cell Migration

1. Hyunggu Hahn
2. Carole Daly
3. Little John
4. Nicole A Perry-Hauser
5. Emmanuel Flores-Espinoza
6. Asuka Inoue
7. Bianca Plouffe
8. Alex Rojas Bie Thomsen

• Curated by eLife

  eLife assessment

  This is a valuable study that provides CCR7-APEX2 proximity labelling mass spectrometry data that is expected to provide new insights into CCR7 signalling partners and pathways. The study is technically solid and easy to follow, however, there are some concerns that many of the highlighted findings are repetitive of prior work and that this is not clearly acknowledged. It would increase the impact of the study if the confirmatory nature of some findings were acknowledged. This is of value to the community, and there are likely multiple opportunities to use the APEX2 data set to extend these findings, strengthen some claims, and even explore a new pathway identified in the APEX2 data set.

Reviewed by eLife

Epigenetic insights into GABAergic development in Dravet Syndrome iPSC and therapeutic implications

1. Jens Schuster
2. Xi Lu
3. Yonglong Dang
4. Joakim Klar
5. Amelie Wenz
6. Niklas Dahl
7. Xingqi Chen

• Curated by eLife

  eLife assessment

  This is a potentially useful study that shows changes in the chromatin landscape of GABAergic neurons in induced pluripotent stem cells (iPSCs) derived from both Dravet Syndrome (DS) patients and healthy donors. The strength of the evidence is currently incomplete because the authors compared iPSCs from different individuals, rather than isogenic controls. A strategy for minimizing variability across cell lines is used, but the explanation is not complete. The revised manuscript adds RNAseq and qPCR measurements of the expression of the gene SCN1A, however these do not appear to agree, perhaps because of the way the qPCR measurements are normalized, and there is no measurement of Nav1.1, the gene product thought to be responsible for the majority of DS cases. Hence the evidence that there is reduced expression of SCN1A or its gene product is not complete and therefore it is difficult to evaluate whether or not the observed epigenetic changes are causal. The work would potentially be of interest to scientists who study development, developmental disorders, and epigenetic contributions to disease.

Reviewed by eLife

Detection of TurboID fusion proteins by fluorescent streptavidin outcompetes antibody signals and visualises targets not accessible to antibodies

1. Johanna Odenwald
2. Bernardo Gabiatti
3. Silke Braune
4. Siqi Shen
5. Martin Zoltner
6. Susanne Kramer

• Curated by eLife

  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 experimental verification of amplification of fluorescence near epitope tags in phase-separated compartments is solid, demonstrating enhanced signal-to-noise compared to immunofluorescence. 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.

Reviewed by eLife