Physiology

SLC4A1 MUTATIONS THAT CAUSE DISTAL RENAL TUBULAR ACIDOSIS ALTER CYTOPLASMIC PH AND CELLULAR AUTOPHAGY

1. Grace Essuman
2. Midhat Rizvi
3. Ensaf Almomani
4. Shahid A. K M. Ullah
5. Sarder M. A. Hasib
6. Forough Chelangarimiyandoab
7. Priyanka Mungara
8. Manfred J. Schmitt
9. Marguerite Hureaux
10. Rosa Vargas-Poussou
11. Nicolas Touret
12. Emmanuelle Cordat

• Curated by eLife

  eLife Assessment

  This work characterizes the function and localization of SLC4A1 variants associated with distal renal tubular acidosis in human patients. Cell culture and limited animal studies provide partial support to the authors' claim that the variants disrupt normal protein degradative flux by alkalinizing the intracellular pH. The study is valuable in providing evidence, albeit limited, for future exploration of the link between intracellular pH regulation by SLC4A1 and kidney cell function in vivo.

Reviewed by eLife

Megakaryocytes assemble a three-dimensional cage of extracellular matrix that controls their maturation and anchoring to the vascular niche

1. Claire Masson
2. Cyril Scandola
3. Jean-Yves Rinckel
4. Fabienne Proamer
5. Emily Janus-Bell
6. Fareeha Batool
7. Naël Osmani
8. Jacky G Goetz
9. Léa Mallo
10. Nathalie Brouard
11. Catherine Léon
12. Alicia Bornert
13. Renaud Poincloux
14. Olivier Destaing
15. Alma Mansson
16. Hong Qian
17. Maxime Lehmann
18. Anita Eckly

• Curated by eLife

  eLife Assessment

  In this revised version, the authors provide a thorough investigation of the interaction of megakaryocytes (MK) with their associated extracellular matrix (ECM) during maturation; they provide compelling evidence that the existence of a dense cage-like pericellular structure containing laminin γ1 and α4 and collagen IV is key to fixing the perisinusoidal localization of MK and preventing their premature intravasation. Adhesion of MK to this ECM cage is dependent on integrin beta1 and beta3 expressed by MK. This strong conclusion is based on the use of state-of-the art techniques such as the use of primary murine bone marrow MK cultures, mice lacking ECM receptors, namely integrin beta1 and beta3 null mice, as well as high-resolution 2D and 3D imaging. The study provides valuable insight into the role of cell-matrix interactions in MK maturation and provides an interesting model with practical implications for the fields of hemostasis and thrombosis

Reviewed by eLife, preLights

Loss of the alternative calcineurin variant CnAβ1 enhances brown adipocyte differentiation and drives metabolic overactivation through FoxO1 activation

1. Elísabet Bello-Arroyo
2. Blanca Rubio
3. Alfonso Mora
4. Marina López-Olañeta
5. Jesús M. Gómez-Salinero
6. Laura Ramos
7. Carlos G. Sánchez-Cabezudo
8. Emilio Camafeita
9. Lorena Cusso
10. Manuel Desco
11. Nolwenn Joffin
12. Johanne Le Coq
13. Jasminka Boskovic
14. Kathryn A. McGurk
15. James S. Ware
16. Paul J. R. Barton
17. Jesús Vázquez
18. Philipp E. Scherer
19. Guadalupe Sabio
20. María Victoria Gómez-Gaviro
21. Enrique Lara-Pezzi

Reviewed by Review Commons

Transient hypoxia followed by progressive reoxygenation is required for efficient skeletal muscle repair through Rev-ERBα modulation

1. Marie Quétin
2. Audrey Der Vartanian
3. Christelle Dubois
4. Juliette Berthier
5. Marine Ledoux
6. Stéphanie Michineau
7. Bernadette Drayton-Libotte
8. Athanassia Sotiropoulos
9. Frédéric Relaix
10. Marianne Gervais

Reviewed by Review Commons

Probing relaxed myosin states in hypertrophic cardiomyopathy by second harmonic-generation microscopy

1. Giulia Arecchi
2. Marica Dente
3. Weikang Ma
4. Beatrice Scellini
5. Nicoletta Piroddi
6. Marina Scardigli
7. Jingyuan Yu
8. Jing Zhao
9. Riccardo Cicchi
10. Ryo Kinegawa
11. Caroline Muellenbroich
12. Corrado Poggesi
13. Cecilia Ferrantini
14. Thomas C Irving
15. Michael Regnier
16. Leonardo Sacconi
17. Chiara Tesi

• Curated by eLife

  eLife Assessment

  Arecchi et al. demonstrate that polarized second-harmonic generation microscopy can be used to probe the ON/OFF states of myosin in both permeabilized and intact muscle, making this key measurement accessible to a greater number of labs. This has the potential to help with the study of disease-causing mutations and our understanding of drug function. The methodology is well defined, and the results are important; however, whilst this is overall a convincing study, there are some limitations to the interpretation of the data.

Reviewed by eLife

Cellular characterization of the mouse collecting lymphatic vessels reveals that lymphatic muscle cells are the innate pacemaker cells

1. Scott D Zawieja
2. Grace A Pea
3. Sarah E Broyhill
4. Advaya Patro
5. Karen H Bromert
6. Charles E Norton
7. Hae J Kim
8. Sathesh K Sivasankaran
9. Min Li
10. Jorge A Castorena-Gonzalez
11. Bernard T Drumm
12. Michael J Davis

• Curated by eLife

  eLife Assessment

  This manuscript aims to identify the pacemaker cells in the lymphatic collecting vessels - the cells that initiate the autonomous action potentials and contractions needed to drive lymphatic pumping. Through the exemplary use of existing approaches (genetic deletions and cytosolic calcium detection in multiple cell types), the authors convincingly determine that lymphatic muscle cells are the origin of the action potential that triggers lymphatic contraction. The inclusion of scRNAseq and membrane potential data enhances a tremendous study. This fundamental discovery establishes a new standard for the field of lymphatic physiology.

Reviewed by eLife

Cell-autonomous and non-cell-autonomous effects of arginase-II on cardiac aging

1. Duilio M Potenza
2. Xin Cheng
3. Guillaume Ajalbert
4. Andrea Brenna
5. Marie-Noelle Giraud
6. Aurelien Frobert
7. Stephane Cook
8. Kirsten D Mertz
9. Zhihong Yang
10. Xiu-Fen Ming

• Curated by eLife

  eLife Assessment

  This study provides fundamental information on how Arg-II participates in cardiac aging. The phenotypic data provide convincing evidence of non-cell-autonomous contributions to aging-related pathologies. Overall, the study highlights the importance of intercellular signaling in maintaining cardiac health during aging.

Reviewed by eLife

TRPV4 activation by TGFβ2 enhances cellular contractility and drives ocular hypertension

1. Christopher Nass Rudzitis
2. Monika Lakk
3. Ayushi Singh
4. Sarah N Redmon
5. Denisa Kirdajová
6. Yun-Ting Tseng
7. Michael L De Ieso
8. W Daniel Stamer
9. Samuel Herberg
10. David Krizaj

• Curated by eLife

  eLife Assessment

  This fundamental work extends our understanding of the role of TGFβ2 as a modulator of mechanosensing in the eye and identifies the TRPV4 ion channel as a common regulator of Trabecular Meshwork (TM) contractility and pathological OHT and the data and evidence provided are convincing. This work will clearly be of interest to researchers investigating the role of mechanosensors in the TM and may underpin future research into treatments that aim to lower intra ocular pressure. This work will additionally be of interest to the growing field of researchers investigating the regulation of force sensing via ion channels and their roles in health and disease, in particular the ion channel TRPV4.

Reviewed by eLife

A whole-animal phenotypic drug screen identifies suppressors of atherogenic lipoproteins

1. Daniel J Kelpsch
2. Liyun Zhang
3. James H Thierer
4. Kobe Koren
5. Urmi Kumar
6. Yuki Lin
7. Monica R Hensley
8. Mira Sohn
9. Jun O Liu
10. Thomas Lectka
11. Jeff S Mumm
12. Steven A Farber

• Curated by eLife

  eLife Assessment

  In this important study, the authors have performed a zebrafish drug screen to identify suppressors of atherogenic lipoproteins. They utilize a well-established LipoGlo assay to find molecules that modulate these lipoproteins, identifying 49 potential hits. They perform some validation experiments, including studies linking enoxolone to its likely inhibitory effect on a specific transcription factor, HNF4alpha. Overall, the results are convincing and robust, and will open up new areas of exploration for those investigators interested in in vivo lipid biology.

Reviewed by eLife

The denitrosylase SCoR2 controls cardioprotective metabolic reprogramming

1. Zachary W Grimmett
2. Rongli Zhang
3. Hua-Lin Zhou
4. Qiuying Chen
5. Dawson Miller
6. Zhaoxia Qian
7. Justin Lin
8. Riti Kalra
9. Steven S Gross
10. Walter J Koch
11. Richard T Premont
12. Jonathan S Stamler

• Curated by eLife

  eLife Assessment

  This study presents compelling evidence that the denitrosylase SCoR2 regulates cardioprotective metabolic reprogramming in the heart following ischemia/reperfusion injury. The findings are supported by a novel multi-omics approach and the integration of mouse and human data, which provides valuable insights into S-nitrosylation and cardiac metabolism. However, some conclusions remain limited by unresolved methodological issues that warrant clarification.

Reviewed by eLife