Cell Biology

Feedback regulation by the RhoA-specific GEF ARHGEF17 regulates actomyosin network disassembly

1. Vasundhara Rao
2. Benjamin Grädel
3. Lucien Hinderling
4. Jakobus Van Unen
5. Olivier Pertz

Reviewed by preLights

Neurons enhance blood–brain barrier function via upregulating claudin-5 and VE-cadherin expression due to glial cell line-derived neurotrophic factor secretion

1. Lu Yang
2. Zijin Lin
3. Ruijing Mu
4. Wenhan Wu
5. Hao Zhi
6. Xiaodong Liu
7. Hanyu Yang
8. Li Liu

• Curated by eLife

  eLife assessment

  This revised study presents valuable evidence that a combination of endothelial cells, astrocytes, and neuroblastoma cells of human origin can integrate to form an in vitro brain blood barrier, that recapitulates key aspects of its natural counterpart, especially at short times. Convincingly, the mechanism by which neuroblastoma-secreted GDNF increases Claudin-5 and VE-cadherin is described. To substantiate the role of GDNF in vivo, authors demonstrated that knock-down of this neurotrophic factor, increased the permeability of the brain blood barrier in mice. This in vitro system can be used to study the permeability of the human brain blood barrier to different drugs.

Reviewed by eLife

Cardiac glycosides restore autophagy flux in an iPSC-derived neuronal model of WDR45 deficiency

1. Apostolos Papandreou
2. Nivedita Singh
3. Lorita Gianfrancesco
4. Dimitri Budinger
5. Katy Barwick
6. Alexander Agrotis
7. Christin Luft
8. Ying Shao
9. An-Sofie Lenaerts
10. Allison Gregory
11. Suh Young Jeong
12. Penelope Hogarth
13. Susan Hayflick
14. Serena Barral
15. Janos Kriston-Vizi
16. Paul Gissen
17. Manju A Kurian
18. Robin Ketteler

• Curated by eLife

  eLife assessment

  This valuable manuscript reports alterations in autophagy present in dopaminergic neurons differentiated from iPSCs of patients with WDR45 mutations. The authors identified compounds that improved the defects present in mutant cells by generating isogenic iPSC without the mutation and performing an automated drug screening. The methodological approaches are solid, but the claims still need to be completed; showing the effects of the identified compounds on iron-related alterations is crucial. The effects of these drugs in vivo would be a great addition to the study.

Reviewed by eLife

Hundreds of myosin 10s are pushed to the tips of filopodia and could cause traffic jams on actin

1. Julia Shangguan
2. Ronald S Rock

• Curated by eLife

  eLife assessment

  The manuscript proposes an alternative method by SDS-PAGE calibration of Halo-Myo10 signals to quantify myosin molecules in filopodia and discusses different scenarios regarding myosin 10 working models to explain intracellular diffusion and targeting to filopodia. Overall, the paper is elegantly written and the methodology is valuable in its descriptive potential as these are key numbers to know to ultimately decipher the cellular mechanism of Myo10 action as well as understand the molecular composition of a Myo10-generated filopodium. The evidence for the conclusions is compelling, but there are limitations to this study which should be kept in mind when applying this method to other systems.

Reviewed by eLife

Reactive oxygen species suppress phagocyte surveillance by oxidizing cytoskeletal regulators

1. Iuliia Ferling
2. Steffen Pfalzgraf
3. Lea Moutounet
4. Lanhui Qiu
5. Yumeng Li
6. Yuhuan Zhou
7. Sergio Grinstein
8. Spencer A Freeman

• Curated by eLife

  eLife assessment

  In this study, Ferling and colleagues provide convincing evidence demonstrating that myeloid cells exert distinct, cargo-dependent responses during and after phagocytosis. These important findings establish previously unrecognized insights into the function(s) of myeloid cells in immunosurveillance and are thus likely to be broadly impactful across the spectrum of biomedical disciplines including immunology and cell biology. Notwithstanding these clear strengths of the article, some minor issues were noted pertinent to the relative opaqueness of the mechanisms underpinning context-specific RhoA activation.

Reviewed by eLife

Multi-tissue proteomics identifies a link between satellite DNA organization and heritable transposon repression in Drosophila

1. Ankita Chavan
2. Lena Skrutl
3. Federico Uliana
4. Melanie Pfister
5. Franziska Brändle
6. Laszlo Tirian
7. Delora Baptista
8. Dominik Handler
9. David Burke
10. Anna Sintsova
11. Pedro Beltrao
12. Julius Brennecke
13. Madhav Jagannathan

Reviewed by Review Commons

APEX-based proximity labeling in Plasmodium identifies a membrane protein with dual functions during mosquito infection

1. Jessica Kehrer
2. Dominik Ricken
3. Leanne Strauss
4. Emma Pietsch
5. Julia M. Heinze
6. Friedrich Frischknecht

Reviewed by Review Commons

Oversized cells activate global proteasome-mediated protein degradation to maintain cell size homeostasis

1. Shixuan Liu
2. Ceryl Tan
3. Chloe Melo-Gavin
4. Miriam B Ginzberg
5. Ron Blutrich
6. Nish Patel
7. Michael Rape
8. Kevin G Mark
9. Ran Kafri

• Curated by eLife

  Evaluation Summary:

  Kafri and colleagues assess the contribution of protein degradation to the cell size-dependent accumulation of total protein. As cells get too big, the efficiency of cell growth decreases, which the authors propose is due to increased protein degradation in larger cells. This is an interesting and novel mechanism, and its discovery is potentially useful for future research on understanding and controlling cell growth, though the data could be further strengthened and clarified to support the conclusions.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

The role of ER exit sites in maintaining P-body organization and transmitting ER stress response during Drosophila melanogaster oogenesis

1. Samantha N. Milano
2. Livia V. Bayer
3. Julie J. Ko
4. Caroline E. Casella
5. Diana P. Bratu

Reviewed by preLights

Reorganization of the flagellum scaffolding induces a sperm standstill during fertilization

1. Martina Jabloñski
2. Guillermina M Luque
3. Matias Gomez Elias
4. Claudia Sanchez Cardenas
5. Xinran Xu
6. Jose L de La Vega Beltran
7. Gabriel Corkidi
8. Alejandro Linares
9. Victor Abonza
10. Aquetzalli Arenas-Hernandez
11. María DP Ramos-Godinez
12. Alejandro López-Saavedra
13. Dario Krapf
14. Diego Krapf
15. Alberto Darszon
16. Adán Guerrero
17. Mariano G Buffone

• Curated by eLife

  eLife assessment

  This important work substantially advances our understanding of sperm motility regulation during fertilization process by uncovering the midpiece/mitochondria contraction associated with motility cessation and structural changes in the midpiece actin network as its mode of action involved. The evidence supporting the conclusion is solid, with rigorous live cell imaging using state-of-art microscopy, although more functional analysis of the midpiece/mitochondria contraction would have further strengthened the study. The work will be of broad interest to cell biologists working on the cytoskeleton, mitochondria, cell fusion, and fertilization.

Reviewed by eLife