Cell Biology

Allosteric modulation of the CXCR4:CXCL12 axis by targeting receptor nanoclustering via the TMV-TMVI domain

1. Eva M García-Cuesta
2. Pablo Martínez
3. Karthik Selvaraju
4. Gabriel Ulltjärn
5. Adrián Miguel Gómez Pozo
6. Gianluca D'Agostino
7. Sofia Gardeta
8. Adriana Quijada-Freire
9. Patricia Blanco Gabella
10. Carlos Roca
11. Daniel del Hoyo
12. Rodrigo Jiménez-Saiz
13. Alfonso García-Rubia
14. Blanca Soler Palacios
15. Pilar Lucas
16. Rosa Ayala-Bueno
17. Noelia Santander Acerete
18. Yolanda Carrasco
19. Carlos Oscar Sorzano
20. Ana Martinez
21. Nuria E Campillo
22. Lasse D Jensen
23. Jose Miguel Rodriguez Frade
24. César Santiago
25. Mario Mellado

• Curated by eLife

  eLife assessment

  This is an important study that describes an elegant modelling driven approach to design of allosteric antagonists for CXCR4 that have a selective effect on receptor nanocluster formation, cell polarisation and chemotaxis, but spare binding of CXCL12 to the receptor and inhibition of adenylate cyclase. This enables selective targeting of processes dependent upon cell polarisation and chemotaxis without impacting signalling effects and may avoid some of the toxicity associated with antagonists that target CXCL12 binding and thus block all CXCR4 signalling. The revised manuscript offers convincing evidence to support the claims. The modelling work is better described and additional data has been presented that better illustrates the unique features of the new antagonist. The in vivo studies in the zebrafish model open a path to studies in mammalian models.

Reviewed by eLife

The actomyosin system is essential for the integrity of the endosomal system in bloodstream form Trypanosoma brucei

1. Fabian Link
2. Sisco Jung
3. Xenia Malzer
4. Felix Zierhut
5. Antonia Konle
6. Alyssa Borges
7. Christopher Batters
8. Monika Weiland
9. Mara Poellmann
10. An Binh Nguyen
11. Johannes Kullmann
12. Claudia Veigel
13. Markus Engstler
14. Brooke Morriswood

• Curated by eLife

  eLife assessment

  This important study builds on a previous publication, demonstrating that T. brucei has a continuous endomembrane system, which probably facilitates high rates of endocytosis. Using a range of cutting-edge approaches, the authors present compelling evidence that an actomyosin system, with the myosin TbMyo1 as an active molecular motor, is localized close to and can associate with the endosomal system in the bloodstream form of Trypanosoma brucei. It shows convincingly that both actin and Myo I play a role in the organization and integrity of the endosomal system: both RNAi-mediated depletion of Myo1, and treatment of the cells with latrunculin A resulted in endomembrane disruption. This work should be of interest to cell biologists and microbiologists working on the cytoskeleton, and unicellular eukaryotes.

Reviewed by eLife, Arcadia Science

Epigenetic insights into GABAergic development in Dravet Syndrome iPSC and therapeutic implications

1. Jens Schuster
2. Xi Lu
3. Yonglong Dang
4. Joakim Klar
5. Amelie Wenz
6. Niklas Dahl
7. Xingqi Chen

• Curated by eLife

  eLife assessment

  This is a potentially useful study that shows changes in the chromatin landscape of GABAergic neurons in induced pluripotent stem cells (iPSCs) derived from both Dravet Syndrome (DS) patients and healthy donors. The strength of the evidence is currently incomplete because the authors compared iPSCs from different individuals, rather than isogenic controls. A strategy for minimizing variability across cell lines is used, but the explanation is not complete. The revised manuscript adds RNAseq and qPCR measurements of the expression of the gene SCN1A, however these do not appear to agree, perhaps because of the way the qPCR measurements are normalized, and there is no measurement of Nav1.1, the gene product thought to be responsible for the majority of DS cases. Hence the evidence that there is reduced expression of SCN1A or its gene product is not complete and therefore it is difficult to evaluate whether or not the observed epigenetic changes are causal. The work would potentially be of interest to scientists who study development, developmental disorders, and epigenetic contributions to disease.

Reviewed by eLife

Detection of TurboID fusion proteins by fluorescent streptavidin outcompetes antibody signals and visualises targets not accessible to antibodies

1. Johanna Odenwald
2. Bernardo Gabiatti
3. Silke Braune
4. Siqi Shen
5. Martin Zoltner
6. Susanne Kramer

• Curated by eLife

  eLife assessment

  This valuable study demonstrates how proximity labeling with streptavidin can be used to boost fluorescence signals in otherwise hard-to-label regions of cells. The experimental verification of amplification of fluorescence near epitope tags in phase-separated compartments is solid, demonstrating enhanced signal-to-noise compared to immunofluorescence. This study will be of particular interest to those using correlative light and electron microscopy or expansion microscopy when the signal is limiting or inaccessible.

Reviewed by eLife

Membrane Curvature Promotes ER-PM Contact Formation via Junctophilin-EHD Interactions

1. Yang Yang
2. Luis A. Valencia
3. Chih-Hao Lu
4. Melissa L. Nakamoto
5. Ching-Ting Tsai
6. Chun Liu
7. Huaxiao Yang
8. Wei Zhang
9. Zeinab Jahed
10. Wan-Ru Lee
11. Francesca Santoro
12. Jen Liou
13. Joseph C. Wu
14. Bianxiao Cui

Reviewed by preLights

Distinct trafficking routes of polarized and non-polarized membrane cargoes in Aspergillus nidulans

1. Georgia Maria Sagia
2. Xenia Georgiou
3. Georgios Chamilos
4. George Diallinas
5. Sofia Dimou

Reviewed by Review Commons

Mitochondrial Apolipoprotein MIC26 is a metabolic rheostat regulating central cellular fuel pathways

1. Melissa Lubeck
2. Ritam Naha
3. Yulia Schaumkessel
4. Philipp Westhoff
5. Anja Stefanski
6. Patrick Petzsch
7. Kai Stühler
8. Karl Köhrer
9. Andreas P. M. Weber
10. Ruchika Anand
11. Andreas S. Reichert
12. Arun Kumar Kondadi

Reviewed by Review Commons

Atlas of Fshr expression from novel reporter mice

1. Hongqian Chen
2. Hui-Qing Fang
3. Jin-Tao Liu
4. Shi-Yu Chang
5. Li-Ben Cheng
6. Ming-Xin Sun
7. Jian-Rui Feng
8. Ze-Min Liu
9. Yong-Hong Zhang
10. Clifford J Rosen
11. Peng Liu

• Curated by eLife

  eLife assessment

  These valuable findings develop a mouse model with trackable fusion Fshr protein, which will be of use to the field. The animal model helps to elucidate the expression and function of the FSH receptor in extra-gonadal tissues. The strength of the evidence is solid in most parts, although additional validation of the localization data would strengthen the study considerably.

Reviewed by eLife

Cytosolic and endoplasmic reticulum chaperones inhibit wt-p53 to increase cancer cells' survival by refluxing ER-proteins to the cytosol

1. Salam Dabsan
2. Gali Zur
3. Naim Abu-Freha
4. Shahar Sofer
5. Iris Grossman-Haham
6. Ayelet Gilad
7. Aeid Igbaria

Reviewed by Review Commons

Mechanisms of cilia regeneration in Xenopus multiciliated epithelium in vivo

1. Venkatramanan G. Rao
2. Vignesharavind Subramanianbalachandar
3. Magdalena M. Magaj
4. Stefanie Redemann
5. Saurabh S. Kulkarni

Reviewed by Review Commons, Arcadia Science