Cell Biology

DIO-SPOTlight Transgenic Mouse to Functionally Monitor Protein Synthesis Regulated by the Integrated Stress Response

1. Matthew L Oliver
2. Zachary F Caffall
3. Callie B Eatman
4. Timothy D Faw
5. Nicole Calakos

• Curated by eLife

  eLife Assessment

  In this manuscript, the authors describe the creation of a transgenic mouse expressing a reporter for Integrated Stress Response (ISR) activation in a CRE-dependent manner. Reliable tools for detecting ISR activation in situ are lacking, so this manuscript describes a potentially valuable tool that builds on and overcomes some of the limitations of a similar viral vector described by the authors in a previous publication. Solid evidence suggests that distinct populations of cells (ChAT) in the nervous system are marked by some level of ISR activation, and that the mouse could be most helpful as a screen for cell types in which the ISR is particularly active, although it would be difficult to draw conclusions from the reporter alone. Additional validations of the reporter activity in situ will further strengthen the manuscript.

Reviewed by eLife

Mechanisms of PP2A-Ankle2 dependent nuclear reassembly after mitosis

1. Jingjing Li
2. Xinyue Wang
3. Laia Jordana
4. Éric Bonneil
5. Victoria Ginestet
6. Momina Ahmed
7. Mohammed Bourouh
8. Cristina Mirela Pascariu
9. T Martin Schmeing
10. Pierre Thibault
11. Vincent Archambault

• Curated by eLife

  eLife Assessment

  This is an important study that reports the mechanism by which Ankle2 (LEM4 in humans) interacts with and recruits PP2A and the ER protein Vap33 to promote BAF dephosphorylation and mediate nuclear membrane reformation, using Drosophila as their model. Using Ankle2 mutants, they find that the ER protein Vap33 is key for the normal interphase localisation of Ankle2/LEM4 and also impacts on the function of Ankle2/LEM4 during mitosis. The conclusions on the subcellular localization of Ankle2 are drawn from overexpression of constructs. Overall, the authors use a variety of complementary techniques and provide convincing evidence to support the claims and advance our knowledge in the field of mitosis and nuclear envelope biology.

Reviewed by eLife

Small molecule modulator of neuronal lysosome positioning and function resolves Alzheimer’s Disease-linked pathologies in cultured human neurons

1. Amanda M. Snead
2. Sruchi Patel
3. Mia Krout
4. Ryan S. Hippman
5. Gabrielle Smith
6. Diya Dileep
7. Nitya Chagoor
8. Rachel Shi
9. Ricardo Linares
10. Andrew Dobria
11. Stephanie M. Cologna
12. Camerron Crowder
13. Leslie N. Aldrich
14. Swetha Gowrishankar

Reviewed by PREreview

TET2-mediated epigenetic modification promotes stress senescence of pancreatic β cells in type 2 diabetes mellitus

1. Weijuan Cai
2. Qingqing Song
3. Xiaoqing Mo
4. Huaqian Li
5. Yuling Song
6. Liang Yin

• Curated by eLife

  eLife Assessment

  This is a useful study that seeks to address the role of the TET family of DNA demethylation enzymes in pancreatic beta cell senescence in the context of type 2 diabetes (T2DM). Although the concepts are novel and of interest, the study presents incomplete evidence to fully support its main conclusions.

Reviewed by eLife

Loss of ErbB3 redirects Integrin β1 from early endosomal recycling to secretion in extracellular vesicles

1. Dorival Mendes Rodrigues-Junior
2. Ana Rosa Sáez-Ibáñez
3. Takeshi Terabayashi
4. Nina Daubel
5. Taija Mäkinen
6. Olof Idevall-Hagren
7. Aristidis Moustakas
8. Ingvar Ferby

Reviewed by Review Commons

Myristoylated Neuronal Calcium Sensor-1 captures the preciliary vesicle at distal appendages

1. Tomoharu Kanie
2. Roy Ng
3. Keene L Abbott
4. Niaj Mohammad Tanvir
5. Esben Lorentzen
6. Olaf Pongs
7. Peter K Jackson

• Curated by eLife

  eLife assessment

  The identification of NCS1 as a distal appendage protein that captures preciliary vesicles has important implications for understanding the early steps of ciliary assembly. Furthermore, the work has important implications for the broader understanding of NCS1, which prior to this work was focused on roles in neurotransmission, but now must be considered in a broader context. The investigators used a variety of state-of-the-art methodologies, and the conclusions are convincingly supported by the experimental data. This work will be of interest to cell biologists studying ciliary assembly, human geneticists exploring the pathology of cilia as well as neurobiologists studying NCS1.

Reviewed by eLife

Single-molecule tracking reveals the dynamics of Ipl1 recruitment to the kinetochores and spindles in S. cerevisiae

1. Nitesh Kumar Podh
2. Ayan Das
3. Akriti Kumari
4. Kirti Garg
5. Rashmi Yadav
6. Kirti Kashyap
7. Sahil Islam
8. Anupam Gupta
9. Gunjan Mehta

Reviewed by Review Commons

Pharmacologic activation of integrated stress response kinases inhibits pathologic mitochondrial fragmentation

1. Kelsey R Baron
2. Samantha Oviedo
3. Sophia Krasny
4. Mashiat Zaman
5. Rama Aldakhlallah
6. Prerona Bora
7. Prakhyat Mathur
8. Gerald Pfeffer
9. Michael J Bollong
10. Timothy E Shutt
11. Danielle A Grotjahn
12. R Luke Wiseman

• Curated by eLife

  eLife Assessment

  This important study identifies a new class of small molecules that activate the integrated stress response (ISR) via the kinase HRI. Convincing evidence, including the image analysis pipeline, indicates that two of these compounds promote mitochondrial elongation and protect against mitochondrial fragmentation caused by chemical stress conditions or by genetic alterations. These findings open an avenue for new strategies for mitochondrial dysfunction targeting linked to ISR alterations.

Reviewed by eLife

Catalytic growth in a shared enzyme pool ensures robust control of centrosome size

1. Deb Sankar Banerjee
2. Shiladitya Banerjee

• Curated by eLife

  eLife Assessment

  This valuable work suggests a new physical model of centrosome maturation: a catalytic growth model with a shared enzyme pool. The authors provide compelling evidence to show that the model is able to reproduce various experimental results such as centrosome size scaling with cell size and centrosome growth curves in C. elegans, and that the final centrosome size is more robust to differences in initial centrosome size. While direct experimental support for this theory is currently lacking, the authors propose concrete experiments that could distinguish their shared-enzyme model from previously proposed alternatives.

Reviewed by eLife

Lysine demethylase 4A is a centrosome‐associated protein required for centrosome integrity and genomic stability

1. Pratim Chowdhury
2. Xiaoli Wang
3. Richard I. Han
4. Manga Motrapu
5. Ashley G. Boice
6. Yuya Nakatani
7. Sofia Vargas‐Hernandez
8. Julia F. Love
9. Claude Chew
10. Sandra L. Grimm
11. Dereck Mezquita
12. Frank M. Mason
13. Elisabeth D. Martinez
14. Cristian Coarfa
15. Cheryl L. Walker
16. Anna‐Karin Gustavsson
17. Ruhee Dere

Reviewed by Review Commons