Cell Biology

Noncanonical amino acid incorporation enables minimally disruptive labeling of stress granule and TDP-43 proteinopathy

1. Hao Chen
2. Haocheng Wang
3. Yuning Lu
4. Peng Chen
5. Zhongfan Zheng
6. Tao Zhang
7. Jiou Wang

• Curated by eLife

  eLife Assessment

  The revised version of the paper demonstrates that a genetic code expansion to tag two ALS proteins associated with stress granules is useful and convincingly evaluates the utility of the genetic code expansion in this context. The data is solid and demonstrates the feasibility of using ANAP-fluorescence for live cell imaging.

Reviewed by eLife

Syntaxin11 Deficiency Inhibits CRAC Channel Priming to Suppress Cytotoxicity and Gene Expression in T Lymphocytes

1. Sritama Datta
2. Abhikarsh Gupta
3. Kunal Mukesh Jagetiya
4. Resmi Bera
5. Vikas Tiwari
6. Atharva Rahul Yande
7. Megumi Yamashita
8. Abdul Rishad
9. Vishal Malik
10. Sreejith Raran-Kurussi
11. Sandra Ammann
12. Mohammad Shahrooei
13. Kalyaneswar Mandal
14. Ramanathan Sowdhamini
15. Murali Prakriya
16. Adish Dani
17. Monika Vig

• Curated by eLife

  eLife Assessment

  This study reports a novel function for syntaxin 11, a specialized SNARE protein critical for the immune system whose mutations cause familial hemophagocytic lymphohistiocytosis type 4. The data convincingly show that depletion of STX11 impairs store-operated calcium entry in Jurkat T cells and that this defect is recapitulated in primary cells from a patient suffering from the disease; the authors further show that the syntaxin interacts with the pore subunit of the ORAI1 channel and propose that it primes the channel by promoting the assembly of multimers before activation by its endogenous ligand, the ER Ca2+ sensing protein STIM1. This is a conceptually important claim that challenges the prevailing view that all structural transitions in ORAI1 are STIM-driven. The data are high-quality and broadly consistent with the interpretation, but alternative mechanisms for the defects are not considered; additional work should rule out vesicular trafficking, discuss other mechanisms, and address methodological issues.

Reviewed by eLife

The functional maturation of mouse spermatozoa is underpinned by global remodeling of the cellular phosphoproteome

1. David A. Skerrett-Byrne
2. Amanda L. Anderson
3. Raffaele Teperino
4. Nathan D. Burke
5. Elizabeth G. Bromfield
6. Matthew D. Dun
7. Valérie Gailus-Durner
8. Helmut Fuchs
9. Susan Marschall
10. Martin Hrabě de Angelis
11. Sean J. Humphrey
12. Brett Nixon

Reviewed by Review Commons

Cell size modulates ferroptosis susceptibility

1. Evgeny Zatulovskiy
2. Magdalena B Murray
3. Shuyuan Zhang
4. Scott J Dixon
5. Jan M Skotheim

• Curated by eLife

  eLife Assessment

  This important study highlights how cell size influences various cellular responses, with a particular focus on ferroptosis. The evidence presented is convincing, employing multiple model systems and experimental approaches to support the conclusions. This work will be of significant interest to the fields of cell size, ferroptosis, and cancer biology.

  [Editors' note: this paper was reviewed by Review Commons.]

Reviewed by eLife, Review Commons

The insulin / IGF axis is critically important for controlling gene transcription in the podocyte

1. Jennifer A Hurcombe
2. Lusyan Dayalan
3. Fern Barrington
4. Frédéric Burdet
5. Lan Ni
6. Joseph T Coward
7. Mark Ibberson
8. Paul T Brinkkoetter
9. Martin Holzenberger
10. Aaron Jeffries
11. Sebastian Oltean
12. Gavin I Welsh
13. Richard JM Coward

• Curated by eLife

  eLife Assessment

  This valuable study used genetic and pharmacological manipulations of insulin/IGF signaling to address the role of insulin/IGF axis in the function of renal glomerular podocyte. Solid data are presented to demonstrate that co-inhibition of insulin/IGF signaling in podocytes led to aberrant splicing of mRNAs, which could contribute to the loss of podocytes in vitro and in vivo in mice. In light of the fact that IR/IGF-1R signaling are critically required for normal development and growth in multiple cells and organs, the lack of the assessment of developmental phenotype of podocytes in the mouse model limits the interpretation of the data.

  [Editors' note: this paper was reviewed by Review Commons.]

Reviewed by eLife

Fibroblast alignment coordinates epithelial migration and maintains intestinal tissue integrity

1. Jordi Comelles
2. Aina Abad-Lázaro
3. Verónica Acevedo
4. David Bartolomé-Català
5. Aitor Otero-Tarrazón
6. Anna Esteve-Codina
7. Xavier Hernando-Momblona
8. Eduard Batlle
9. Vanesa Fernández-Majada
10. Elena Martinez

Reviewed by Review Commons

Analysis of cancer mutations introduced into the Drosophila Notch Negative Regulatory Region uncovers a diversity of regulatory outcomes

1. Hideyuki Shimizu
2. Martin Baron

• Curated by eLife

  eLife Assessment

  This important study presents a technically rigorous and carefully controlled analysis of the signalling potential of cancer-associated gain-of-function Notch alleles. The work is clearly presented, and the experiments are robust, comprehensive, and well-controlled. While some data primarily establish the system or report negative findings, the comparative approach in a well-characterized model provides convincing mechanistic evidence for how these Notch variants function. This study will be of interest to researchers in both developmental and cancer biology.

Reviewed by eLife

An ancient transcription factor functions as the master regulator of primary cilia formation

1. Weihua Wang
2. Xiqi Zhang
3. Yaxuan Qiu
4. Xiangrui Meng
5. Sitong Cheng
6. Yutong Chen
7. Siqi Liu
8. Wenhui Chen
9. Jiayan Yi
10. Xiwen You
11. Hongni Liu
12. Junqiao Xing
13. Cheng Xu
14. Haochen Jiang
15. Haibo Wang
16. Guangmei Tian
17. Zhangfeng Hu

• Curated by eLife

  eLife Assessment

  This useful study identified XAP5 as an ancient transcriptional regulator critical for primary ciliogenesis. The evidence supporting the conceptual framework linking evolutionary conservation to functional specialization in primary ciliogenesis remains incomplete. This work will be of interest to developmental biologists and to those studying diseases caused by ciliopathies.

Reviewed by eLife

Spatiotemporal dynamics of DNA repair proteins between the Golgi and nucleus maintain genomic stability

1. George Galea
2. Karolina Kuodyte
3. Muzamil M. Khan
4. Peter Thul
5. Beate Neumann
6. Emma Lundberg
7. Rainer Pepperkok

Reviewed by Review Commons

MORC2 mediates transcriptional regulation through liquid-liquid phase separation

1. Yanshen Zhang
2. Weiya Xu
3. Wenxiu Duan
4. Yu Wei
5. Wenli Jiang
6. Feng Zhu
7. Chengdong Huang
8. Chao Wang
9. Yihui Bi

• Curated by eLife

  eLife Assessment

  This important study has demonstrated that MORC2 undergoes phase separation in cells and established multiple interactions responsible for the phase separation. Upon revision, the data generally provide solid support to the claim that MORC2 condensates are functionally relevant in gene regulation and begins to demonstrate the importance of the physical properties of biological condensates. Nevertheless, there remains some weakness in the connection between condensates and function.

Reviewed by eLife