Cell Biology

Negative regulation of APC/C activation by MAPK-mediated attenuation of Cdc20Slp1 under stress

1. Li Sun
2. Xuejin Chen
3. Chunlin Song
4. Wenjing Shi
5. Libo Liu
6. Shuang Bai
7. Xi Wang
8. Jiali Chen
9. Chengyu Jiang
10. Shuang-min Wang
11. Zhou-qing Luo
12. Ruiwen Wang
13. Yamei Wang
14. Quan-wen Jin

• Curated by eLife

  eLife assessment

  The regulation of mitosis and the dynamics of the mitotic spindle in it are central to cell division with high fidelity and crucial for normal division and development and defects therein can lead to disease. A key component of ensuring the fidelity is the "spindle assembly checkpoint". This valuable study using convincing experimental approaches in fission yeast has revealed novel links between the MAP-kinase signalling pathway modulating the spindle assembly checkpoint.

Reviewed by eLife

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 GDNF 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

Molecular mapping and functional validation of GLP-1R cholesterol binding sites in pancreatic beta cells

1. Affiong I Oqua
2. Kin Chao
3. Liliane El Eid
4. Lisa Casteller
5. Alba Miguéns
6. Sebastian Barg
7. Ben Jones
8. Jorge Bernadino de la Serna
9. Sarah L Rouse
10. Alejandra Tomas

• Curated by eLife

  eLife assessment

  This study presents a valuable finding on the role of cholesterol-binding site on GLP-1 receptors and functionally characterizes the impact of this mutation on receptor behavior in the membrane and downstream signaling. The computational and experimental approaches used in the study to arrive at the conclusions are solid. The clinical ramifications are unclear at this point, but the study is a helpful addition to the scientific community working on receptor biology and drug development.

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. Iris 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

UGGT1-mediated reglucosylation of N -glycan competes with ER-associated degradation of unstable and misfolded glycoproteins

1. Satoshi Ninagawa
2. Masaki Matsuo
3. Deng Ying
4. Shuichiro Oshita
5. Shinya Aso
6. Kazutoshi Matsushita
7. Mai Taniguchi
8. Akane Fueki
9. Moe Yamashiro
10. Kaoru Sugasawa
11. Shunsuke Saito
12. Koshi Imami
13. Yasuhiko Kizuka
14. Tetsushi Sakuma
15. Takashi Yamamoto
16. Hirokazu Yagi
17. Koichi Kato
18. Kazutoshi Mori

• Curated by eLife

  eLife assessment

  This important manuscript demonstrates that UGGT1 is involved in preventing the premature degradation of endoplasmic reticulum (ER) glycoproteins through the re-glucosylation of their N-linked glycans following release from the calnexin/calreticulin lectins. The authors include a wealth of convincing data in support of their findings, although extending these findings to other types of substrates, such as secreted proteins, could further demonstrate the global importance of this mechanism for protein trafficking through the secretory pathway. This will work will be of interest to scientists interested in ER protein quality control, proteostasis, and protein trafficking.

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