Cell Biology

Targeting A-kinase anchoring protein 12 phosphorylation in hepatic stellate cells regulates liver injury and fibrosis in mouse models

1. Komal Ramani
2. Nirmala Mavila
3. Aushinie Abeynayake
4. Maria Lauda Tomasi
5. Jiaohong Wang
6. Michitaka Matsuda
7. Eki Seki

• Curated by eLife

  Evaluation Summary:

  The work is relevant to colleagues who study non-alcoholic fatty liver disease, the most common chronic disease in the world. It starts with steatosis (fat deposition) in the liver and progresses to very devastating stages of liver fibrosis. This study provides novel insight into mechanisms that result in liver inflammation and fibrosis and identifies a novel disease pathway, which is an attractive target for the treatment of liver fibrosis. The study can be improved, especially by refining the quality of microscopic images and techniques of protein chemistry.

  (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

CFAP61 is required for sperm flagellum formation and male fertility in human and mouse

1. Siyu Liu
2. Jintao Zhang
3. Zine Eddine Kherraf
4. Shuya Sun
5. Xin Zhang
6. Caroline Cazin
7. Charles Coutton
8. Raoudha Zouari
9. Shuqin Zhao
10. Fan Hu
11. Selima Fourati Ben Mustapha
12. Christophe Arnoult
13. Pierre F. Ray
14. Mingxi Liu

• Curated by eLife

  Evaluation Summary:

  This manuscript describes a specific role for CFAP61 - a known component of axonemal radial spokes - in formation and function of sperm flagella in the mouse, and identifies CFAP61 as a disease gene linked to male infertility in a human patient. Furthermore, the authors show that CFAP61 interacts with several radial spoke components, including head and stalk regions, as well as with intraflagellar transport proteins. Overall, the quality of the data is high and the mouse work is consistent with a previously published report. The study underscores the physiological importance of CFAP61 in male fertility and will be of interest to cell and structural biologist studying flagella and motile cilia function, as well as to clinicians involved in fertility genetics. The study can serve a starting point to revealing the precise mechanism by which CFAP61 regulates sperm flagella formation and function and for further analysis human patient data.

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

Reviewed by eLife

Systematic analysis of YFP gene traps reveals common discordance between mRNA and protein across the nervous system

1. Joshua S Titlow
2. Maria Kiourlappou
3. Ana Palanca
4. Jeffrey Y Lee
5. Dalia S Gala
6. Darragh Ennis
7. Joyce J S Yu
8. Florence L Young
9. David Miguel Susano Pinto
10. Sam Garforth
11. Helena S Francis
12. Finn Strivens
13. Hugh Mulvey
14. Alex Dallman-Porter
15. Staci Thornton
16. Diana Arman
17. Aino I Järvelin
18. Mary Kay Thompson
19. Ilias Kounatidis
20. Richard M Parton
21. Stephen Taylor
22. Ilan Davis

Reviewed by Review Commons

Actin assembly requirements of the formin Fus1 to build the fusion focus

1. Ingrid Billault-Chaumartin
2. Laetitia Michon
3. Caitlin A. Anderson
4. Sarah E. Yde
5. Cristian Suarez
6. Justyna Iwaszkiewicz
7. Vincent Zoete
8. David R. Kovar
9. Sophie G. Martin

Reviewed by Review Commons

Mettl3-mediated m6A modification of Fgf16 restricts cardiomyocyte proliferation during heart regeneration

1. Fu-Qing Jiang
2. Kun Liu
3. Jia-Xuan Chen
4. Yan Cao
5. Wu-Yun Chen
6. Wan-Ling Zhao
7. Guo-Hua Song
8. Chi-Qian Liang
9. Yi-Min Zhou
10. Huan-Lei Huang
11. Rui-Jin Huang
12. Hui Zhao
13. Kyu-Sang Park
14. Zhenyu Ju
15. Dongqing Cai
16. Xu-Feng Qi

• Curated by eLife

  Evaluation Summary:

  The manuscript identified m6A RNA methylation (via increased m6A writer, Mettl3 expression) as a critical regulator of cardiomyocyte proliferation during the initial regenerative window that was proposed earlier in the mouse heart. The authors have comprehensively profiled Mettl3 expression and Mettl3-dependent m6A regulation during cardiac regeneration using a variety of in vivo models as well as using in vitro primary cardiomyocytes to identify Fgf16 as a key downstream mRNA transcript for m6A RNA modification by Mettl3. Furthermore, they show that m6A-dependent cytoplasmic decay of Fgf16 mRNA in a Ythdf2-dependent pathway is the key underlying mechanism regulating cardiac regeneration in these models. In sum, a well-designed study with new data that shows suppression of a developmentally induced phenomenon as a therapeutic option for inducing cardiac proliferation.

  (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

Overcoming the cytoplasmic retention of GDOWN1 modulates global transcription and facilitates stress adaptation

1. Zhanwu Zhu
2. Jingjing Liu
3. Huan Feng
4. Yanning Zhang
5. Ruiqi Huang
6. Qiaochu Pan
7. Jing Nan
8. Ruidong Miao
9. Bo Cheng

• Curated by eLife

  Evaluation Summary:

  This study identifies two distinct nuclear export elements and a strong cytoplasmic anchoring sequence that restrict transcription factor GDOWN1 to the cytoplasm in normal conditions. The authors identify stress conditions that override this normal control to promote GDOWN1 nuclear localization as part of a protective response. This study will be of interest to the transcriptional regulation field.

  (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

A pulse-chasable reporter processing assay for mammalian autophagic flux with HaloTag

1. Willa Wen-You Yim
2. Hayashi Yamamoto
3. Noboru Mizushima

• Curated by eLife

  Evaluation Summary:

  This paper will be of interest to researchers in the autophagy field. It provides a useful tool to accurately measure autophagy flux, providing a useful alternative to the existing assay. The key claims of the manuscript are well supported by the data, and the approaches used are thoughtful and rigorous.

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

Reviewed by eLife

Combinatorial G x G x E CRISPR screening and functional analysis highlights SLC25A39 in mitochondrial GSH transport

1. Xiaojian Shi
2. Bryn Reinstadler
3. Hardik Shah
4. Tsz-Leung To
5. Katie Byrne
6. Luanna Summer
7. Sarah E. Calvo
8. Olga Goldberger
9. John G. Doench
10. Vamsi K. Mootha
11. Hongying Shen

Reviewed by Biophysics Colab

The SARS-CoV-2 Spike Protein Activates the Epidermal Growth Factor Receptor-Mediated Signaling

1. Abdulrasheed Palakkott
2. Aysha Alneyadi
3. Khalid Muhammad
4. Ali H. Eid
5. Khaled Amiri
6. Mohammed Akli Ayoub
7. Rabah Iratni

Reviewed by ScreenIT

Multiple ciliary localization signals control INPP5E ciliary targeting

1. Dario Cilleros-Rodriguez
2. Raquel Martin-Morales
3. Pablo Barbeito
4. Abhijit Deb Roy
5. Abdelhalim Loukil
6. Belen Sierra-Rodero
7. Gonzalo Herranz
8. Olatz Pampliega
9. Modesto Redrejo-Rodriguez
10. Sarah C Goetz
11. Manuel Izquierdo
12. Takanari Inoue
13. Francesc R Garcia-Gonzalo

• Curated by eLife

  Evaluation Summary:

  This manuscript is of interest to developmental and cell biologists exploring cilia dynamics and ciliopathies. The authors address the molecular mechanisms by which INPP5E, a phosphoinositide phosphatase essential for regulating cilia function, is targeted to the primary cilium of cultured mammalian cells. Using immunoprecipitation, ciliary localization, phosphatase activity assays in combination with structural modelling, the authors identify four motifs important for ciliary localization of INPP5E, and uncover several novel and important interactions with other ciliary proteins providing a likely mechanism for ciliary targeting. The claims are generally well supported by the data, but some additional data acquisition and analysis are required to fully support the authors' conclusions and provide a conceptual advance in the field.

  (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 #3 agreed to share their names with the authors.)

Reviewed by eLife