Cell Biology

Cdc4 phospho-degrons allow differential regulation of Ame1CENP-U protein stability across the cell cycle

1. Miriam Böhm
2. Kerstin Killinger
3. Alexander Dudziak
4. Pradeep Pant
5. Karolin Jänen
6. Simone Hohoff
7. Karl Mechtler
8. Mihkel Örd
9. Mart Loog
10. Elsa Sanchez-Garcia
11. Stefan Westermann

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest to those in the fields of chromosome biology, mitotic regulation, and proteostasis. The authors put forward an interesting model of phosphodegron regulation of kinetochore assembly based on convincing genetic and biochemical data. The novel model will require some additional evidence before it can be considered well-supported, but the paper represents an advance in our knowledge of kinetochore regulation with experiments that are rigorous, well-designed and carefully conducted.

  (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. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Phases of cortical actomyosin dynamics coupled to the neuroblast polarity cycle

1. Chet Huan Oon
2. Kenneth E Prehoda

• Curated by eLife

  Evaluation Summary:

  Oon and Prehoda report pulsatile contraction of apical membrane in the process of Par protein polarization in Drosophila neuroblasts. This explains how/why actin filament was required to localize/polarize Par complex. This very much resembles the observation in C. elegans embryos, and nicely unifies observations across systems.

  (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

Genetic, cellular, and structural characterization of the membrane potential-dependent cell-penetrating peptide translocation pore

1. Evgeniya Trofimenko
2. Gianvito Grasso
3. Mathieu Heulot
4. Nadja Chevalier
5. Marco A Deriu
6. Gilles Dubuis
7. Yoan Arribat
8. Marc Serulla
9. Sebastien Michel
10. Gil Vantomme
11. Florine Ory
12. Linh Chi Dam
13. Julien Puyal
14. Francesca Amati
15. Anita Lüthi
16. Andrea Danani
17. Christian Widmann

• Curated by eLife

  Evaluation Summary:

  Although the role of membrane potential in Cell Permeable Peptides (CPP) translocation has been consistently described in artificial systems, this multi scale study, combining cell biology, genetics and in silico approaches, further extends this topic to a live cell context where it shows that internalization stops when the membrane polarization is decreased by the removal of potassium channels. It proposes an original mechanism of CPP translocation based on water pore formation, which should be of interest for biophysicists, cell biologists and for applications such as drug delivery.

  (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 #2 agreed to share their name with the authors.)

Reviewed by eLife, Review Commons

GSK3 inhibition rescues growth and telomere dysfunction in dyskeratosis congenita iPSC-derived type II alveolar epithelial cells

1. Rafael Jesus Fernandez
2. Zachary JG Gardner
3. Katherine J Slovik
4. Derek C Liberti
5. Katrina N Estep
6. Wenli Yang
7. Qijun Chen
8. Garrett T Santini
9. Javier V Perez
10. Sarah Root
11. Ranvir Bhatia
12. John W Tobias
13. Apoorva Babu
14. Michael P Morley
15. David B Frank
16. Edward E Morrisey
17. Christopher J Lengner
18. F Brad Johnson

• Curated by eLife

  Summary: The investigators' study of human AT2 cells-derived from induced pluripotent stem cells (iAT2 cells) in the presence and absence of a known dyskeratosis congenita (DC) pathogenic variant provides an exceptional model for understanding pathogenesis of pulmonary fibrosis in dyskeratosis congenita (DC) and related telomere biology disorders (TBDs). They provide convincing data demonstrating altered WNT signaling in iAT2 cells with short, dysfunctional telomeres and improved growth of iAT2 cells by GSK3 inhibition but fall short of convincingly showing the latter is due restored telomere end protection. The work should be of interest to those in the fields of telomere biology and the TBDs, lung physiology, WNT signaling and stem cell biology.

Reviewed by eLife

TCR signaling promotes the assembly of RanBP2/RanGAP1-SUMO1/Ubc9 nuclear pore subcomplex via PKC-θ-mediated phosphorylation of RanGAP1

1. Yujiao He
2. Zhiguo Yang
3. Chen-Si Zhao
4. Yu Gong
5. Zhihui Xiao
6. Yun-Yi Li
7. Yiqi Chen
8. Dianying Feng
9. Amnon Altman
10. Yingqiu Li

• Curated by eLife

  Evaluation Summary:

  PKC-theta is known to regulate T cell activation, and this manuscript reveals a novel function of PKC-theta in the regulation of the nuclear pore complexes. The work by He and colleagues reveals that PKC-theta is recruited to the nuclear pore complex wherein it serves to regulate the assembly of key components of the RanBP2 subcomplex of the NPC, which in turn enables the translocation of AP1, NFkB and NFAT into the nucleus. However, these results need to be substantiated by additional experiments or by limiting the breath of 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

CEM500K – A large-scale heterogeneous unlabeled cellular electron microscopy image dataset for deep learning

1. Ryan Conrad
2. Kedar Narayan

• Curated by eLife

  Evaluation Summary:

  This manuscript describes the curation of a training dataset that will be an important resource for developers of new segmentation and deep-learning algorithms for electron microscopy data. The small size of the dataset makes it easy to use, and its broad range of image modalities ensure that the model will be applicable in many situations, making it very useful for the community.

  (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 and Reviewer #2 agreed to share their names with the authors.)

Reviewed by eLife

Adult Stem Cell-derived Complete Lung Organoid Models Emulate Lung Disease in COVID-19

1. Courtney Tindle
2. MacKenzie Fuller
3. Ayden Fonseca
4. Sahar Taheri
5. Stella-Rita Ibeawuchi
6. Nathan Beutler
7. Gajanan D. Katkar
8. Amanraj Claire
9. Vanessa Castillo
10. Moises Hernandez
11. Hana Russo
12. Jason Duran
13. Laura E. Crotty Alexander
14. Ann Tipps
15. Grace Lin
16. Patricia A. Thistlethwaite
17. Ranajoy Chattopadhyay
18. Thomas F. Rogers
19. Debashis Sahoo
20. Pradipta Ghosh
21. Soumita Das

• Curated by eLife

  Evaluation Summary:

  The manuscript by Tindle et al describes generation of adult lung organoids (ALO) from human lung biopsies and their use to study the changes in gene expression as a result of SARS-CoV-2 infection. In this particular case the authors report the presence of AT1, AT2 cells, Basal cells, Goblet cells, Ciliated cells and Club cells. The authors were able to cultivate the cells at the air-liquid interface and to establish cultures of predominately proximal and predominately distal airway cells. The main finding is that proximal cells are more prone to viral infection, while distal cells are governing the exuberant inflammatory response, with both cells required for the exuberant response to occur. Useful information provided by the paper is the analysis gene signatures of various cellular models, in comparison to the infected human lung.

  (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 and Reviewer #2 agreed to share their names with the authors.)

Reviewed by eLife, ScreenIT

CTP and parS coordinate ParB partition complex dynamics and ParA-ATPase activation for ParABS-mediated DNA partitioning

1. James A Taylor
2. Yeonee Seol
3. Jagat Budhathoki
4. Keir C Neuman
5. Kiyoshi Mizuuchi

• Curated by eLife

  Evaluation Summary:

  This manuscript reports carefully executed experiments on the dynamics of ParA-ParB and ParB-ParB interactions. Two main findings are presented: a change in stoichiometry of ParA-ParB interactions upon ligand binding and ligand dependent DNA condensation by ParB. The work is solid, the conclusions are generally well supported by the data, however, the relevance of some of the findings could be established more directly.

  (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

Single-cell transcriptomics defines heterogeneity of epicardial cells and fibroblasts within the infarcted heart

1. Julia Hesse
2. Christoph Owenier
3. Tobias Lautwein
4. Ria Zalfen
5. Jonas F. Weber
6. Zhaoping Ding
7. Christina Alter
8. Alexander Lang
9. Maria Grandoch
10. Norbert Gerdes
11. Jens W. Fischer
12. Gunnar W. Klau
13. Christoph Dieterich
14. Karl Köhrer
15. Jürgen Schrader

• Curated by eLife

  Evaluation Summary:

  The article by Hesse et al. defines heterogeneity of epicardial cells and fibroblasts in a murine model of cardiac injury to analyze the resulting populations through single cell RNA sequencing. Spatial confirmation of associated markers is performed using in-situ RNA hybridization. The work provides new insights into the heterogeneity of epicardial stromal and activated cardiac stromal cells post-injury.

  (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

Misoprostol Treatment Prevents Hypoxia-Induced Cardiac Dysfunction Through a 14-3-3 and PKA regulatory motif on Bnip3

1. Matthew D. Martens
2. Nivedita Seshadri
3. Lucas Nguyen
4. Donald Chapman
5. Elizabeth S. Henson
6. Bo Xiang
7. Landon Falk
8. Arielys Mendoza
9. Sunil Rattan
10. Spencer B. Gibson
11. Richard Keijzer
12. Ayesha Saleem
13. Grant M. Hatch
14. Christine A. Doucette
15. Jason M. Karch
16. Vernon W. Dolinsky
17. Ian M. Dixon
18. Adrian R. West
19. Christof Rampitsch
20. Joseph W. Gordon

Reviewed by Review Commons