Physiology

Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel

1. Xiaoyi Mo
2. Peiyuan Pang
3. Yulin Wang
4. Dexiang Jiang
5. Mengyu Zhang
6. Yang Li
7. Peiyu Wang
8. Qizhi Geng
9. Chang Xie
10. Hai-Ning Du
11. Bo Zhong
12. Dongdong Li
13. Jing Yao

• Curated by eLife

  Evaluation Summary:

  The TRPV2 channel plays essential roles in many cell types in the body, including macrophages and cardiomyocytes, but its physiological mechanisms of activation and regulation remain largely unknown. Mo and collaborators describe a novel regulatory mechanism of TRPV2 channels in which phosphorylation at three different tyrosine residues by JAK1 sensitizes channels to activation by 2-APB and heat, whereas de-phosphorylation by PTPN1 reverses sensitization. Changes in the dynamics of TRPV2 channel phosphorylation could have important physiological consequences in many cell types expressing these channels. The data are of significant importance for the scientific community interested in function und relevance of transient receptor potential ion channels.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their names with the authors.)

Reviewed by eLife

Discovery and functional assessment of a novel adipocyte population driven by intracellular Wnt/β-catenin signaling in mammals

1. Zhi Liu
2. Tian Chen
3. Sicheng Zhang
4. Tianfang Yang
5. Yun Gong
6. Hong-Wen Deng
7. Ding Bai
8. Weidong Tian
9. YiPing Chen

• Curated by eLife

  Evaluation Summary:

  It is becoming increasingly clear that adipocytes are not homogenous, but rather comprise several distinct subtypes with specific physiological functions. This work presents evidence for the surprising finding of a subpopulation of adipocytes displaying non-canonical Wnt signaling. The possible role of these adipocytes in thermogenesis is more ambiguous, and their physiological function remains unclear.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Unbiased proteomics, histochemistry, and mitochondrial DNA copy number reveal better mitochondrial health in muscle of high-functioning octogenarians

1. Ceereena Ubaida-Mohien
2. Sally Spendiff
3. Alexey Lyashkov
4. Ruin Moaddel
5. Norah J MacMillan
6. Marie-Eve Filion
7. Jose A Morais
8. Tanja Taivassalo
9. Luigi Ferrucci
10. Russell T Hepple

• Curated by eLife

  Evaluation Summary:

  This study analyzed muscle protein differences between octogenarian master athletes and non-athletes. The data showed that high physical function in octogenarians was associated with the increased mitochondrial proteome, reduced number of muscle fibers impaired by oxphos, and higher mtDNA copy number. The authors propose that this is one of the mechanisms contributing to better performance in master athletes compared with non-athletes, suggesting that mitochondrial health in skeletal muscle is a key feature in inducing improved physical function in the elderly. This article has the potential to generate a significant impact within the field and will be of interest to a broad audience.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Fibronectin meshwork controls epithelial stem cell fate

1. Soline Estrach
2. Lionel Tosello
3. Floriane S. Tissot
4. Laurence Cailleteau
5. Ludovic Cervera
6. Kim B Jensen
7. Chloé C. Féral

Reviewed by Review Commons

Post-translational modification patterns on β-myosin heavy chain are altered in ischemic and nonischemic human hearts

1. Maicon Landim-Vieira
2. Matthew C Childers
3. Amanda L Wacker
4. Michelle Rodriquez Garcia
5. Huan He
6. Rakesh Singh
7. Elizabeth A Brundage
8. Jamie R Johnston
9. Bryan A Whitson
10. P Bryant Chase
11. Paul ML Janssen
12. Michael Regnier
13. Brandon J Biesiadecki
14. J Renato Pinto
15. Michelle S Parvatiyar

• Curated by eLife

  Evaluation Summary:

  This study reports new post-translational modifications (PTMs) to β-myosin heavy chain, using tissue samples from normal and failing human hearts. Atomistic simulations of myosin molecular dynamics suggest that these PTMs lead to meaningful alterations in structure, solvent exposure, and dynamics of certain regions of the protein. These data and simulations provide a foundation for further work to determine the precise functional significance of β-myosin heavy chain PTMs. The work will be of interest to cell biologists and cardiologists.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Genetic variation of putative myokine signaling is dominated by biological sex and sex hormones

1. Leandro M Velez
2. Cassandra Van
3. Timothy Moore
4. Zhenqi Zhou
5. Casey Johnson
6. Andrea L Hevener
7. Marcus M Seldin

• Curated by eLife

  Evaluation Summary:

  This elegantly performed systems-genetics paper on the predicted human skeletal muscle secretome highlights the importance of sex and sex hormones in regulating myokine expression and predicted cross-tissue effects. Male and female mice lacking estrogen receptor α (Esr1) were used to understand how estrogen signalling affects myokine genes expression. The methods used and data presented in this manuscript can serve as an important resource for other researchers in the field.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Inhibition of the sodium-dependent HCO3- transporter SLC4A4, produces a cystic fibrosis-like airway disease phenotype

1. Vinciane Saint-Criq
2. Anita Guequén
3. Amber R Philp
4. Sandra Villanueva
5. Tábata Apablaza
6. Ignacio Fernández-Moncada
7. Agustín Mansilla
8. Livia Delpiano
9. Iván Ruminot
10. Cristian Carrasco
11. Michael A Gray
12. Carlos A Flores

• Curated by eLife

  Evaluation Summary:

  This paper is of interest to scientists and clinicians within the field of muco-obstructive diseases in the airways, such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). It identifies the sodium-bicarbonate cotransporter SLC4A4 as a key component of the mechanism by which normal airways prevent the formation of sticky mucus and defend theirselves against bacterial and viral infections.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 and Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Adiponectin receptor agonist AdipoRon improves skeletal muscle function in aged mice

1. Priya Balasubramanian
2. Anne E Schaar
3. Grace E Gustafson
4. Alex B Smith
5. Porsha R Howell
6. Angela Greenman
7. Scott Baum
8. Ricki J Colman
9. Dudley W Lamming
10. Gary M Diffee
11. Rozalyn M Anderson

• Curated by eLife

  Evaluation Summary:

  In this manuscript, the authors provide promising results for the treatment of age-related sarcopenia with AdipoRon, a drug that targets the receptors for adiponectin. This is a well done study using an agonist (AdipoRon) involved in lipid and mitochondrial metabolism regulation to mitigate age related muscle loss in mice.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Ca2+ inactivation of the mammalian ryanodine receptor type 1 in a lipidic environment revealed by cryo-EM

1. Ashok R Nayak
2. Montserrat Samsó

• Curated by eLife

  Evaluation Summary:

  Inactivation of ryanodine receptors (RyR1) is an important physiologic phenomenon disruption of which leads to skeletal muscle and heart diseases. By comparing cryoEM structures of RyR1 in closed, open, and inactivated states, this study provides structural insights into RyR1 calcium-dependent inactivation (CDI). The results rationalize how some disease-causing mutations in RyR1 eliminate CDI of the channel. The study will be of interest to ion channel structural biologists and physiologists studying skeletal muscle pathologies.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

A plasma membrane-localized polycystin-1/polycystin-2 complex in endothelial cells elicits vasodilation

1. Charles E MacKay
2. Miranda Floen
3. M Dennis Leo
4. Raquibul Hasan
5. Tessa AC Garrud
6. Carlos Fernández-Peña
7. Purnima Singh
8. Kafait U Malik
9. Jonathan H Jaggar

• Curated by eLife

  Evaluation Summary:

  This study is potentially of high significance to a broad audience of scientists working on vascular reactivity and the role of ion channels in controlling endothelial cell signaling and vessel contractility. The study uses novel Endothelial cell specific knockout mice of Polycystin-1 and 2 (PC1 and PC2) proteins to show the requirement of PC1 and PC2 in flow-mediated vasodilation, how PC-1 and PC-2 interact and that their functions are interdependent. The findings from this study are novel and significant. The animal models used in this study are state of the art and the data overall are of high quality. However, additional data are needed to support the conclusions of the study. Further, additional controls and clarifications are required.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife