Cell Biology

Molecular mapping and functional validation of GLP-1R cholesterol binding sites in pancreatic beta cells

1. Affiong I Oqua
2. Kin Chao
3. Liliane El Eid
4. Lisa Casteller
5. Billy P Baxter
6. Alba Miguéns-Gómez
7. Sebastian Barg
8. Ben Jones
9. Jorge Bernadino de la Serna
10. Sarah L Rouse
11. Alejandra Tomas

• Curated by eLife

  eLife Assessment

  The study presents a valuable finding on the role of cholesterol-binding sites on GLP-1 receptors although the clinical ramifications are unclear and not eminent at this point. Based on the detailed and persuasive responses provided by authors to the concerns raised by reviewers, the revised manuscript is improved substantially and is convincing enough in its scientific merit. The study is a good addition to the scientific community working on receptor biology and drug development for GLP-1 R.

Reviewed by eLife

HNF4α-TET2-FBP1 axis contributes to gluconeogenesis and type 2 diabetes

1. Hongchen Li
2. Xinchao Zhang
3. Xiaoben Liang
4. Shuyan Li
5. Ziyi Cui
6. Xinyu Zhao
7. Kai Wang
8. Bingbing Zha
9. Haijie Ma
10. Ming Xu
11. Lei Lv
12. Yanping Xu

• Curated by eLife

  eLife Assessment

  Zhang et al. present important findings that reveal a new role for TET2 in controlling glucose production in the liver, showing that both fasting and a high-fat diet increase TET2 levels, while its absence reduces glucose production. TET2 works with HNF4α to activate the FBP1 gene upon glucagon stimulation, while metformin disrupts TET2-HNF4α interaction, lowering FBP1 levels and improving glucose homeostasis. The results are convincing and expand our understanding of gluconeogenesis regulation.

Reviewed by eLife

A novel SUN1-ALLAN complex coordinates segregation of the bipartite MTOC across the nuclear envelope during rapid closed mitosis in Plasmodium

1. Mohammad Zeeshan
2. Igor Blatov
3. Ryuji Yanase
4. David JP Ferguson
5. Sarah L Pashley
6. Zeinab Chahine
7. Yoshiki Yamaryo Botté
8. Akancha Mishra
9. Baptiste Marché
10. Suhani Bhanvadia
11. Molly Hair
12. Sagar Batra
13. Robert Markus
14. Declan Brady
15. Andrew Bottrill
16. Sue Vaughan
17. Cyrille Y Botté
18. Karine Le Roch
19. Anthony A Holder
20. Eelco C Tromer
21. Rita Tewari

• Curated by eLife

  eLife Assessment

  In Plasmodium male gametocytes, rapid nuclear division occurs with an intact nuclear envelope, requiring precise coordination between nuclear and cytoplasmic events to ensure proper packaging of each nucleus into a developing gamete. This valuable study characterizes two proteins involved in the formation of Plasmodium berghei male gametes. By integrating live-cell imaging, ultrastructural expansion microscopy, and proteomics, this study convincingly identifies SUN1 and its interaction partner ALLAN as crucial nuclear envelope components in male gametogenesis. A role for SUN1 in membrane dynamics and lipid metabolism is less well supported. The results are of interest for general cell biologists working on unusual mitosis pathways.

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

Reviewed by eLife, Review Commons

Heme’s relevance genuine? Re-visiting the roles of TANGO2 homologs including HRG-9 and HRG-10 in C. elegans

1. Sarah E Sandkuhler
2. Kayla S Youngs
3. Laura Owlett
4. Monica B Bandora
5. Aaliya Naaz
6. Euri S Kim
7. Lili Wang
8. Andrew P Wojtovich
9. Vandana A Gupta
10. Michael Sacher
11. Samuel J Mackenzie

• Curated by eLife

  eLife Assessment

  This useful study provides incomplete evidence that TANGO2 homologs, including HRG-9 and HRG-10, are not heme chaperones but play a role in cellular bioenergetics and oxidative stress homeostasis. While outstanding strengths include the use of different model systems, genetic tools, and behavioral assays, there are weaknesses in the data presented for the conclusions drawn. Due to the differences in experimental protocols between this study and the previous work reported by Sun et al., it is insufficient to rule out the role of TANGO2 as a heme chaperone, and furthermore, the authors provide only indirect evidence for the role of TANGO2 in bioenergetic and oxidative stress pathways. Nevertheless, this study paves the way for future mechanistic studies addressing the mechanisms of how TANGO2 regulates oxidative stress independent of its previously demonstrated role as a heme chaperone.

Reviewed by eLife

Chronic stress antagonizes formation of Stress Granules

1. Yuichiro Adachi
2. Allison M. Williams
3. Masashi Masuda
4. Yutaka Taketani
5. Paul J. Anderson
6. Pavel Ivanov

Reviewed by preLights

Profiling the physiological impact of aberrant folded-state protein filamentation in cells

1. Tal Levin
2. Hector Garcia-Seisdedos
3. Arseniy Lobov
4. Matthias Wojtynek
5. Alexander Alexandrov
6. Ghil Jona
7. Dikla Levi
8. Ohad Medalia
9. D. Emmanuel Levy

Reviewed by Review Commons

Functional redundancy and formin-independent localization of tropomyosin isoforms in Saccharomyces cerevisiae

1. Anubhav Dhar
2. VT Bagyashree
3. Sudipta Biswas
4. Jayanti Kumari
5. Amruta Sridhara
6. B Jeevan Subodh
7. Shashank Shekhar
8. Saravanan Palani

Reviewed by Review Commons

Reprograming gene expression in “hibernating” C. elegans involves the IRE-1/XBP-1 pathway

1. Melanie L Engelfriet
2. Yanwu Guo
3. Andreas Arnold
4. Eivind Valen
5. Rafal Ciosk

• Curated by eLife

  eLife Assessment

  This useful study reveals that as C. elegans, a poikilothermic ("cold-blooded") animal, adapt to cold (4ºC), they display a drastic reduction in translation (assessed by polysome profiling and SUNSET). The remaining translation (by ribo-seq) correlates with mRNA levels (by RNA-seq), and the changes in gene expression at least partially require IRE-1, an established endoplasmic reticulum stress sensor. The reviewers consider the data assessing global translation and RNA expression upon cold exposure and the data demonstrating the requirement of ire-1 to be solid, but the conclusion that "transcription" is the major regulatory step and "lipid changes" can be a signal for IRE-1 activation in cold adapted worms needs substantially more evidence. Overall, this study demonstrated a good correlation between translation and RNA levels and yielded an inventory of gene changes as C. elegans adapt to cold, and will be of general interest to researchers interested in stress response and cold adaptation.

Reviewed by eLife

Nucleoporin Nup153 docks the splicing machinery to the nuclear pore for efficient mRNA processing

1. IJ de Castro
2. L Schuster
3. C Patiño-Gomez
4. D Glavas
5. A Udupa
6. M Ríos Vázquez
7. T Symens
8. G Tulcan
9. J Heinze
10. Heras J de las
11. Robert Reinhardt
12. Jorge Trojanowski
13. H Harz
14. G Stumberger
15. H Leonhardt
16. E Schirmer
17. S Saka
18. V Laketa
19. M Lusic

Reviewed by Review Commons

Mutations that prevent phosphorylation of the BMP4 prodomain impair proteolytic maturation of homodimers leading to lethality in mice

1. Hyung-seok Kim
2. Mary L Sanchez
3. Joshua Silva
4. Heidi L Schubert
5. Rebecca Dennis
6. Christopher P Hill
7. Jan L Christian

• Curated by eLife

  eLife Assessment

  This fundamental work presents two clinically relevant BMP4 mutations that contribute to vertebrate development. The compelling evidence, both from wet lab and AI generated predictions, supports that the site-specific cleavage at the BMP4 pro-domain precisely regulates its function and provides mechanistic insight how homodimers and heterodimers behave differently. The work will be of board interest to researchers working on growth factor signaling mechanisms and vertebrate development.

Reviewed by eLife