Cell Biology

Trabid patient mutations impede the axonal trafficking of adenomatous polyposis coli to disrupt neurite growth

1. Daniel Frank
2. Maria Bergamasco
3. Michael J Mlodzianoski
4. Andrew Kueh
5. Ellen Tsui
6. Cathrine Hall
7. Georgios Kastrappis
8. Anne Kathrin Voss
9. Catriona McLean
10. Maree Faux
11. Kelly L Rogers
12. Bang Tran
13. Elizabeth Vincan
14. David Komander
15. Grant Dewson
16. Hoanh Tran

• Curated by eLife

  eLife assessment

  This study defines the roles for two different missense mutations observed in patients in the Trabid/ZRANB1 gene associated in children with a range of congenital disorders including reduced brain size. The study is important because the findings have theoretical or practical implications beyond a single subfield, as the study of DUB and cytoskeletal alterations have implications for neurodevelopment broadly. The methods are convincing as they utilize appropriate and validated methodology in line with current state-of-the-art by incorporating knock-in mice of the patient mutations. Many of the reviewer comments were focused on potential next experiments, rather than on evaluation of the data at hand, and the authors have considered these as future studies. The work as presented suggests critical roles for Trabid in the STRIPAK complex mediating APC deubiquitylation.

Reviewed by eLife

Heterogeneous non-canonical nucleosomes predominate in yeast cells in situ

1. Zhi Yang Tan
2. Shujun Cai
3. Alex J Noble
4. Jon K Chen
5. Jian Shi
6. Lu Gan

• Curated by eLife

  eLife assessment

  This important paper exploits new cryo-EM tomography tools to examine the state of chromatin in situ. The experimental work is meticulously performed, with a vast amount of data collected, with convincing interpretation of possible nucleosomal structures in yeast. The majority of these nucleosomes appear not to possess stable octameric configurations. Although it cannot be excluded that there could be an unknown bias in class detection, we agree that the authors have gone as far as is possible, given constraints in current technology and analysis, to support their model. Despite the provocative nature of this report, it is our hope that such work will spark debate, and further the development of exciting new tools that can interrogate the dynamic nature of the nucleosome, and its associated functions in situ.

Reviewed by eLife

Pharmacological inhibition of CLK2 activates YAP by promoting alternative splicing of AMOTL2

1. Maya L Bulos
2. Edyta M Grzelak
3. Chloris Li-Ma
4. Emily Chen
5. Mitchell Hull
6. Kristen A Johnson
7. Michael J Bollong

• Curated by eLife

  eLife assessment

  This paper reports important findings on a potent activator of the YAP pathway, demonstrating its mechanism through alternative splicing changes. The authors provide convincing evidence to support their claims. This research is of interest to biologists studying alternative splicing or the Hippo pathway, with significant implications for medical research.

Reviewed by eLife

Palmitoylation of proteolipid protein M6 promotes tricellular junction assembly in epithelia of Drosophila

1. Raphael Schleutker
2. Stefan Luschnig

Reviewed by Review Commons

Mitochondrial electron transport chain, ceramide, and coenzyme Q are linked in a pathway that drives insulin resistance in skeletal muscle

1. Alexis Diaz-Vegas
2. Søren Madsen
3. Kristen C Cooke
4. Luke Carroll
5. Jasmine XY Khor
6. Nigel Turner
7. Xin Y Lim
8. Miro A Astore
9. Jonathan C Morris
10. Anthony S Don
11. Amanda Garfield
12. Simona Zarini
13. Karin A Zemski Berry
14. Andrew P Ryan
15. Bryan C Bergman
16. Joseph T Brozinick
17. David E James
18. James G Burchfield

• Curated by eLife

  eLife assessment

  This important study highlights a potential connection between fatty acid intrusion into myocytes and increases in mitochondrial ceramide that cause deficits in coenzyme Q and consequent insulin resistance. The authors primarily use the L6 myocyte model, which may not fully recapitulate in vivo conditions, however, the manuscript shows compelling data in mice that substantially supports the L6 cell results. Overall, this study provides a strong framework for a compelling pathway of myocyte dysfunction and for continued efforts to test the important hypotheses that are presented.

Reviewed by eLife

LRRC23 truncation impairs radial spoke 3 head assembly and sperm motility underlying male infertility

1. Jae Yeon Hwang
2. Pengxin Chai
3. Shoaib Nawaz
4. Jungmin Choi
5. Francesc Lopez-Giraldez
6. Shabir Hussain
7. Kaya Bilguvar
8. Shrikant Mane
9. Richard P Lifton
10. Wasim Ahmad
11. Kai Zhang
12. Jean-Ju Chung

• Curated by eLife

  eLife assessment

  This study provides valuable findings on a causative relationship between LRRC23 mutations and male infertility due to asthenozoospermia. The evidence supporting the conclusions is solid. This work will be of interest to biomedical researchers who work on sperm biology and non-hormonal male contraceptive development.

Reviewed by eLife

Exonuclease Xrn1 regulates TORC1 signaling in response to SAM availability

1. Madeline M. McGinnis
2. Benjamin M. Sutter
3. Samira Jahangiri
4. Benjamin P. Tu

• Curated by eLife

  eLife assessment

  This study in budding yeast (S. cerevisiae) presents important findings demonstrating that the exonuclease Xrn1 regulates autophagy in response to methionine deprivation through effects on TORC1. There is solid evidence that the impact of Xrn1 on TORC1 is contingent on its catalytic activity rather than the degradation of any specific category of mRNAs. A major strength is the novel mechanism, in which Xrn1 modulates the nucleotide-binding state of the Gtr1/2 complex.

Reviewed by eLife

The stress-induced lincRNA JUNI is a critical factor for cancer cell survival whose interactome is a prognostic signature in clear cell renal cell carcinoma

1. Vikash Kumar
2. Xavier Sabaté-Cadenas
3. Isha Soni
4. Esther Stern
5. Carine Vias
6. Doron Ginsberg
7. Carlos Romá-Mateo
8. Rafael Pulido
9. Martin Dodel
10. Faraz K. Mardakheh
11. Iddo Z. Ben-Dov
12. Alena Shkumatava
13. Eitan Shaulian

Reviewed by Review Commons

Structured RhoGEF recruitment drives myosin II organization on large exocytotic vesicles

1. Kumari Kamalesh
2. Dagan Segal
3. Ori Avinoam
4. Eyal D. Schejter
5. Ben-Zion Shilo

Reviewed by preLights

Phosphorylation bar-coding of free fatty acid receptor 2 is generated in a tissue-specific manner

1. Natasja Barki
2. Laura Jenkins
3. Sara Marsango
4. Domonkos Dedeo
5. Daniele Bolognini
6. Louis Dwomoh
7. Aisha M Abdelmalik
8. Margaret Nilsen
9. Manon Stoffels
10. Falko Nagel
11. Stefan Schulz
12. Andrew B Tobin
13. Graeme Milligan

• Curated by eLife

  eLife assessment

  In this study, the authors present important tools for monitoring distinct tissue-specific patterns of agonist-induced Free Fatty Acid receptor 2 phosphorylation. The work includes several validation experiments, which provide convincing evidence that will be beneficial for the scientific community.

Reviewed by eLife