Cell Biology

Formation of multinucleated osteoclasts depends on an oxidized species of cell surface-associated La protein

1. Evgenia Leikina
2. Jarred M Whitlock
3. Kamran Melikov
4. Wendy Zhang
5. Michael P Bachmann
6. Leonid Chernomordik

• Curated by eLife

  eLife assessment

  This manuscript provides an important advance in our understanding of the molecular events that promote osteoclast fusion. Compelling data support the conclusion that an oxidized form of the ubiquitous protein La promotes osteoclast fusion following enrichment at the cell surface of osteoclast progenitors. These data improve our understanding of the processes that regulate bone resorption and will be of broad interest to researchers in the fields of cell biology and musculoskeletal physiology.

Reviewed by eLife

Circular RNA HMGCS1 sponges MIR4521 to aggravate type 2 diabetes-induced vascular endothelial dysfunction

1. Ming Zhang
2. Guangyi Du
3. Lianghua Xie
4. Yang Xu
5. Wei Chen

• Curated by eLife

  eLife assessment

  This study presents important findings linking circHMGCS1 and miR-4521 in diabetes-induced vascular endothelial dysfunction. Overall, the evidence supporting the claims of the authors is convincing. The work will be of interest to biomedical scientists working with cardiovascular and/or RNA biology, particularly those studying diabetes.

Reviewed by eLife

S-acylation of NLRP3 provides a nigericin sensitive gating mechanism that controls access to the Golgi

1. Daniel M Williams
2. Andrew A Peden

• Curated by eLife

  eLife assessment

  This important paper implicates S-acylation of Cys-130 in recruitment of the inflammasome receptor NLRP3 to the Golgi, and it provides convincing evidence that S-acylation plays a key role in response to the stress induced by nigericin treatment. While Cys-130 does seem to play a previously unappreciated role in membrane association of NLRP3, further work will be needed to clarify the details of the mechanism.

Reviewed by eLife

Time-resolved proximity proteomics uncovers a membrane tension-sensitive caveolin-1 interactome at the rear of migrating cells

1. Eleanor Martin
2. Rossana Girardello
3. Gunnar Dittmar
4. Alexander Ludwig

• Curated by eLife

  eLife assessment

  This important study uses convincing time-resolved proximity proteomics, validated with proximity ligation assays, to provide new insight into mechanical regulation of caveolin-1 complexes that form in migrating cells. Solid follow up experiments reveal a reciprocal relationship between mechanosensitive caveolae and RhoGTPase signalling in migrating cells, but evidence supporting a direct link between the newly identified factors with a specific caveolae subpopulation remains incomplete at this stage.

Reviewed by eLife

A MSTNDel73C mutation with FGF5 knockout sheep by CRISPR/Cas9 promotes skeletal muscle myofiber hyperplasia

1. Ming-Ming Chen
2. Yue Zhao
3. Kun Yu
4. Xue-Ling Xu
5. Xiao-Sheng Zhang
6. Jin-Long Zhang
7. Su-Jun Wu
8. Zhi-Mei Liu
9. Yi-Ming Yuan
10. Xiao-Fei Guo
11. Shi-Yu Qi
12. Guang Yi
13. Shu-Qi Wang
14. Huang-Xiang Li
15. Ao-Wu Wu
16. Guo-Shi Liu
17. Shou-Long Deng
18. Hong-Bing Han
19. Feng-Hua Lv
20. Di Lian
21. Zheng-Xing Lian

• Curated by eLife

  eLife assessment

  The authors present a useful analysis of the phenotype of sheep in which the muscle developmental regulator myostatin has been mutated in a FGF5 knockout background. The goal was to produce sheep with a "double-muscled" phenotype, yet the genetically engineered sheep exhibited meat with a smaller cross-sectional area and higher number of muscle fibers. The work extends the extensive body of knowledge already published in this area. The authors provide evidence using in vitro experiments that Fosl1 regulates myogenesis, but the strength of evidence relating to the muscle phenotype and underlying cellular and molecular mechanism remains incomplete.

Reviewed by eLife

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

Unique ultrastructural organization of human rod photoreceptors

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

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 Poellmann
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