Cell Biology

An unconventional interaction interface between the peroxisomal targeting factor Pex5 and Eci1 enables PTS1 independent import

1. Lior Peer
2. Nadav Elad
3. Orly Dym
4. Asa Tirosh
5. Jossef Jacobovitch
6. Shira Albeck
7. Maya Schuldiner
8. Yoav Peleg
9. Einat Zalckvar

Reviewed by Review Commons

scRNA-seq and scATAC-seq reveal that Sertoli cell mediates spermatogenesis disorders through stage-specific communications in non-obstructive azoospermia

1. Shimin Wang
2. Hongxian Wang
3. Bicheng Jin
4. Hongli Yan
5. Qingliang Zheng
6. Dong Zhao

• Curated by eLife

  eLife Assessment

  This study provides valuable scRNA-seq and scATAC-seq data for testicular tissues from patients with spermatogenesis disorders. By examining the transcriptomic and epigenetic changes in Sertoli cells, the authors uncovered key regulatory mechanisms underlying male infertility and identified potential therapeutic targets. While some of the cellular profiling results are convincing, the analyses for differential profiling of NOA cases and epigenomics data remain incomplete.

Reviewed by eLife

Novel mechanism for tubular injury in nephropathic cystinosis

1. Swastika Sur
2. Maggie Kerwin
3. Silvia Pineda
4. Poonam Sansanwal
5. Tara K Sigdel
6. Marina Sirota
7. Minnie M Sarwal

• Curated by eLife

  eLife Assessment

  This important study addresses the idea that defective lysosomal clearance might be causal to renal dysfunction in cystinosis. With mostly solid data, the authors observe that restoring expression of vATPase subunits and treatment with Astaxanthin ameliorate mitochondrial function in a model of renal epithelial cells, opening opportunities for translational application to humans.

Reviewed by eLife

Maturation and detoxification of synphilin-1 inclusion bodies regulated by sphingolipids

1. Xiuling Cao
2. Xiang Wu
3. Lei Zhao
4. Ju Zheng
5. Xuejiao Jin
6. Xinxin Hao
7. Joris Winderickx
8. Shenkui Liu
9. Lihua Chen
10. Beidong Liu

• Curated by eLife

  eLife Assessment

  By combining Synthetic Genetic Array (SGA) analysis with state-of-the-art imaging techniques, this study provides strong evidence that sphingolipid metabolism controls the maturation of Parkinson's disease-associated Synphilin-1 inclusion bodies (SY1 IBs) on the mitochondrial surface in a yeast model. The authors present compelling proof that perturbing the sphingolipid metabolic pathway leads to delayed SY1 IB maturation and enhanced SY1-triggered toxicity. Altogether, the authors show the important role of sphingolipid metabolism in the detoxification process of misfolded proteins by facilitating large IB formation on the mitochondrial outer membrane.

Reviewed by eLife

Ezrin defines TSC complex activation at endosomal compartments through EGFR–AKT signaling

1. Giuliana Giamundo
2. Daniela Intartaglia
3. Eugenio Del Prete
4. Elena Polishchuk
5. Fabrizio Andreone
6. Marzia Ognibene
7. Sara Buonocore
8. Bruno Hay Mele
9. Francesco Giuseppe Salierno
10. Jlenia Monfregola
11. Dario Antonini
12. Paolo Grumati
13. Alessandra Eva
14. Rossella De Cegli
15. Ivan Conte

• Curated by eLife

  eLife Assessment

  Giamundo et al. present fundamental data with new insights into the role of Ezrin, a major membrane-actin linker that assembles signaling complexes, in the spatial regulation of EGF signaling mediators. The use of multiple state-of-the-art microscopy techniques, multiple cell lines and inhibitors, together with in vivo models convincingly supports the majority of their conclusions. The findings are helpful for understanding EGF/mTOR signal transduction and support a critical role for the scaffolding protein Ezrin in the upstream regulation of EGFR/AKT activity, TSC subcellular localization and mTORC1 signaling. These findings contribute substantially to understanding how endo-lysosomal signaling are regulated, alterations which are implicated in many human diseases.

Reviewed by eLife

Non-muscle myosin II regulates presynaptic actin assemblies and neuronal mechanobiology in Drosophila

1. Biljana Ermanoska
2. Jonathan Baets
3. Avital A. Rodal

Reviewed by Review Commons

A ‘torn bag mechanism’ of small extracellular vesicle release via limiting membrane rupture of en bloc released amphisomes (amphiectosomes)

1. Tamás Visnovitz
2. Dorina Lenzinger
3. Anna Koncz
4. Péter M Vizi
5. Tünde Bárkai
6. Krisztina V Vukman
7. Alicia Galinsoga
8. Krisztina Németh
9. Kelsey Fletcher
10. Zsolt I Komlósi
11. Csaba Cserép
12. Ádám Dénes
13. Péter Lőrincz
14. Gábor Valcz
15. Edit I Buzas

• Curated by eLife

  eLife Assessment

  In this study, the authors present compelling data illustrating a potential mechanism for a hitherto not described form of extracellular vesicle biogenesis. Their model suggests that small extracellular vesicles are secreted from cells within larger vesicles, termed amphiectosomes, which subsequently rupture to release their smaller vesicle contents. This discovery represents an important advancement in the field.

Reviewed by eLife

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