Cell Biology

Optogenetic control of a GEF of RhoA uncovers a signaling switch from retraction to protrusion

1. Jean de Seze
2. Maud Bongaerts
3. Benoit Boulevard
4. Mathieu Coppey

• Curated by eLife

  eLife Assessment

  This important study combines compelling experiments with optogenetic actuation and convincing theory to understand how signalling proteins control the switch between cell protrusion and retraction, two essential processes in single cell migration. The authors examine the importance of the basal concentration and recruitment dynamics of a guanine exchange factor (GEF) on the activity of the downstream effectors RhoA and Cdc42, which control retraction and protrusion. The experimental and theoretical evidence provides a model of RhoA's involvement in both protrusion and retraction and shows that these complex processes are highly dependent on the concentration and activity dynamics of the components.

Reviewed by eLife

Spatial confinement induces reciprocating migration of epidermal keratinocytes and forms triphasic epithelia

1. Takuma Nohara
2. Junichi Kumamoto
3. Yosuke Mai
4. Mayuna Shimano
5. Sora Kato
6. Hiroyuki Kitahata
7. Hideki Nakamura
8. Shota Takashima
9. Mika Watanabe
10. Masaharu Nagayama
11. Tsukasa Oikawa
12. Hideyuki Ujiie
13. Ken Natsuga

• Curated by eLife

  eLife Assessment

  In this manuscript the authors established a novel three-dimensional culture system for stratified epithelia that allows epithelial cells to undergo epithelial-to-mesenchymal transition (EMT) and subsequent mesenchymal-to-epithelial transition (MET) while migrating through a membrane with 3.0-µm micropores, and, thus, provides a valuable tool to study EMT and possibly wound regeneration or metastasis. Furthermore, a set of experiments provides solid data suggesting that TGF beta signaling and actin polymerization promote movement of epithelial cells into the pores, while Piezo1 and Keratin 6 prevent keratinocyte migration and EMT.

Reviewed by eLife

A delta-tubulin/epsilon-tubulin/Ted protein complex is required for centriole architecture

1. Rachel Pudlowski
2. Lingyi Xu
3. Ljiljana Milenkovic
4. Chandan Kumar
5. Katherine Hemsworth
6. Zayd Aqrabawi
7. Tim Stearns
8. Jennifer T Wang

• Curated by eLife

  eLife Assessment

  The study by Pudlowski et al. shows that a previously-identified protein complex, composed of delta- and epsilon-tubulin together with TEDC1 and TEDC2, functions in generating centriolar triplet microtubules, and that this is crucial for the proper formation of centriolar subdomains and the stability of centrioles throughout the cell cycle. This is an important study that advances our understanding of centriole biogenesis and structure and is supported by convincing evidence based on knockout cell lines, immunoprecipitation, and ultrastructure expansion microscopy. The work is of interest to cell biologists, in particular researchers with interest in centrosome biology.

Reviewed by eLife

Roles of Srs2/PARI-family DNA helicases in NoCut checkpoint signaling and abscission regulation

1. Monica Dam
2. David F. Moreno
3. Nicola Brownlow
4. Audrey Furst
5. Coralie Spiegelhalter
6. Manuel Mendoza

Reviewed by Review Commons

A cryo-electron microscopy structure of yeast Pex5 in complex with a cargo uncovers a novel binding interface

1. Lior Peer
2. Orly Dym
3. Nadav Elad
4. Asa Tirosh
5. Jossef Jacobovitch
6. Ehud Sivan
7. Mor Angel
8. Shira Albeck
9. Maya Schuldiner
10. Yoav Peleg
11. 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. Hongxiang 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.

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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