Biophysics

ATP-release pannexin channels are gated by lysophospholipids

1. Erik Henze
2. Russell N Burkhardt
3. Bennett William Fox
4. Tyler J Schwertfeger
5. Eric Gelsleichter
6. Kevin Michalski
7. Lydia Kramer
8. Margret Lenfest
9. Jordyn M Boesch
10. Hening Lin
11. Frank C Schroeder
12. Toshimitsu Kawate

• Curated by eLife

  eLife Assessment

  Pannexin (Panx) channels are a family of poorly understood large-pore channels that mediate the release of substrates like ATP from cells, yet the physiological stimuli that activate these channels remain poorly understood. The study by Henze et al. describes an elegant approach wherein activity-guided fractionation of mouse liver led to the discovery that lysophospholipids (LPCs) activate Panx1 and Panx2 channels expressed in cells or reconstituted into liposomes. The authors provide compelling evidence that LPC-mediated activation of Panx1 is involved in joint pain and that Panx1 channels are required for the established effects of LPC on inflammasome activation in monocytes, suggesting that Panx channels play a role in inflammatory pathways. Overall, this important study reports a previously unanticipated mechanism wherein LPCs directly activate Panx channels. The work will be of interest to scientists investigating phospholipids, Panx channels, purinergic signalling and inflammation.

  [Editors' note: this paper was reviewed and curated by Biophysics Colab]

• Curated by Biophysics Colab

  Evaluation Statement (5 February 2025)

  Pannexin (Panx) channels are a family of poorly understood large-pore channels that mediate the release of substrates like ATP from cells, yet the physiological stimuli that activate these channels remain poorly understood. The preprint by Henze et al. describes an elegant approach wherein activity-guided fractionation of mouse liver led to the discovery that lysophospholipids (LPCs) activate Panx1 and Panx2 channels expressed in cells or reconstituted into liposomes. The authors provide evidence that LPC-mediated activation of Panx1 is involved in joint pain and that Panx1 channels are required for the established effects of LPC on inflammasome activation in monocytes, suggesting that Panx channels play a role in inflammatory pathways. Overall, this important study reports a previously unanticipated mechanism wherein LPCs directly activate Panx channels.

  Biophysics Colab recommends this study to scientists investigating phospholipids, Panx channels, purinergic signalling and inflammation.

  Biophysics Colab has evaluated this study as one that meets the following criteria:

  • Rigorous methodology
  • Transparent reporting
  • Appropriate interpretation

  (This evaluation refers to version 3 of this preprint, which has been revised in response to peer review of versions 1 and 2.)

Reviewed by eLife, Biophysics Colab

A mathematical model clarifies the ABC Score formula used in enhancer-gene prediction

1. Joseph Nasser
2. Kee-Myoung Nam
3. Jeremy Gunawardena

• Curated by eLife

  eLife Assessment

  This important study dissects the mathematical and biological assumptions underlying the commonly used Activity-by-Contact model of enhancer action in transcriptional regulation. The authors provide a convincing mathematical analysis that links this (mostly phenomenological) model to concrete molecular mechanisms of enhancer function. This work provides a strong foundation from which to analyze a broad swath of genome-wide data such as that generated by CRISPRi screens.

Reviewed by eLife

Geometry effects on protein mobility in a synapse

1. Simon Dannenberg
2. Sofiia Reshetniak
3. Sarah Mohammadinejad
4. Silvio O. Rizzoli
5. Stefan Klumpp

Reviewed by PREreview

Arp2/3-mediated bidirectional actin assembly by SPIN90 dimers in metazoans

1. Tianyang Liu
2. Luyan Cao
3. Miroslav Mladenov
4. Guillaume Romet-Lemonne
5. Michael Way
6. Carolyn A. Moores

Reviewed by Arcadia Science

The mechanism of DRB7.2:DRB4 mediated sequestering of endogenous inverted-repeat dsRNA precursors in plants

1. Sneha Paturi
2. Debadutta Patra
3. Priti Chanda Behera
4. Ramdas Aute
5. Nilam Waghela
6. Priyadarshan Kinatukara
7. Mandar V Deshmukh

• Curated by eLife

  eLife Assessment

  The manuscript provides valuable findings in the field for understanding the RNAi regulation in plants at the molecular level with a model of how DRB7.2 and DRB4 form a heterodimer and protect dsRNA from DICER activity. The presented data provide a solid basis for the model, but certain measurements could benefit from replicates for robust statistics.

Reviewed by eLife

Kinetic regulation of kinesin’s two motor domains coordinates its stepping along microtubules

1. Yamato Niitani
2. Kohei Matsuzaki
3. Erik Jonsson
4. Ronald D Vale
5. Michio Tomishige

• Curated by eLife

  eLife Assessment

  This study provides compelling evidence that kinesin's stepping mechanism is governed by strain-induced conformational changes in its nucleotide-binding pockets. Using pre-steady state kinetics and single-molecule assays, the authors demonstrate that the neck linker's conformation differentially modulates nucleotide affinity and detachment rates, establishing an asynchronous chemo-mechanical cycle that prevents simultaneous detachment. Supported by cryo-EM structural data, the work presents an important advance in our understanding of kinesin's hand-over-hand movement.

  [Editors' note: this paper was reviewed by Review Commons.]

Reviewed by eLife, Review Commons

Load-based divergence in the dynamic allostery of two TCRs recognizing the same pMHC

1. Ana Cristina Chang-Gonzalez
2. Aoi Akitsu
3. Robert J Mallis
4. Matthew J Lang
5. Ellis L Reinherz
6. Wonmuk Hwang

• Curated by eLife

  eLife Assessment

  This useful study reports detailed molecular dynamics (MD) simulations of T-cell receptors (TCRs) in complex with a peptide/MHC complex, for a better understanding of the mechanism of T-cell activation. The MD simulations provide solid evidence supporting that different TCRs can respond mechanically in different ways upon binding to the same pMHC complex. The analyses are systematic and provide testable predictions that can be evaluated by future mutagenesis and force microscopy studies.

Reviewed by eLife

Deletion of PIEZO1 in adult cardiomyocytes accelerates cardiac aging and causes premature death

1. Ze-Yan Yu
2. Yang Guo
3. Scott Kesteven
4. Delfine Cheng
5. Hanzhou Lei
6. Jianxin Wu
7. Evelyn Nadar
8. Peter Macdonald
9. Munira Xaymardan
10. Charles D. Cox
11. Michael P. Feneley
12. Boris Martinac

Reviewed by preLights

A role for JAK2 in mediating cell surface GHR-PRLR interaction

1. Chen Chen
2. Jing Jiang
3. Tejeshwar C Rao
4. Ying Liu
5. Tatiana T Marquez Lago
6. Stuart J Frank
7. André Leier

• Curated by eLife

  eLife Assessment

  This is an important study that characterizes a surprising interaction between two different cytokine/hormone receptors using nanoscale resolution (dSTORM) microscopy. The study provides solid evidence that the interaction is ligand-dependent, and is mediated by the receptor-associated intracellular signalling molecule JAK2. While at present limited to growth hormone and prolactin receptors in a limited number of cell lines, there are potentially broad implications for cytokine signalling, as such JAK2-mediated interactions could occur between a range of different cytokines. Moreover, the specific hormone interactions shown in the manuscript may have significant implications for understanding how these hormones can have differential effects in breast cancer, under different conditions.

Reviewed by eLife

Distinct activation mechanisms of CXCR4 and ACKR3 revealed by single-molecule analysis of their conformational landscapes

1. Christopher T Schafer
2. Raymond F Pauszek
3. Martin Gustavsson
4. Tracy M Handel
5. David P Millar

• Curated by eLife

  eLife Assessment

  This manuscript describes the characterization of the conformational dynamics of two chemokine receptors at the single-molecule level using FRET. The authors make a convincing case for attributing the distinct interaction and pharmacology of the two receptors to differences in their conformational energy landscape. These important findings will be of interest to scientists working on activation mechanisms of GPCRs and signal transduction.

Reviewed by eLife