Cell Biology

CLEM Site , a software for automated phenotypic screens using light microscopy and FIB-SEM

1. José M. Serra Lleti
2. Anna M. Steyer
3. Nicole L. Schieber
4. Beate Neumann
5. Christian Tischer
6. Volker Hilsenstein
7. Mike Holtstrom
8. David Unrau
9. Robert Kirmse
10. John M. Lucocq
11. Rainer Pepperkok
12. Yannick Schwab

Reviewed by Review Commons

Identification of epigenetic modulators as determinants of nuclear size and shape

1. Andria C Schibler
2. Predrag Jevtic
3. Gianluca Pegoraro
4. Daniel L Levy
5. Tom Misteli

• Curated by eLife

  eLife Assessment:

  In this manuscript the authors describe targeted, imaging-based RNAi screens to identify novel modulators of nuclear size and shape — two traits that are diagnostic and prognostic for many human diseases including cancers. The work provides novel insights into how and what dictates nuclear morphology, further decoupling key different components of lamins, chromatin, and the nuclear envelope, but there are some notable concerns regarding the scoring approach applied in the screen and hit validation. The authors also provide new evidence that lamin A may directly bind to (modified) histone H3 and how histone H3 disease mutations impact nuclear shape; this aspect of the manuscript would benefit from a more thorough analysis.

  (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

Mechanical control of the mammalian circadian clock via YAP/TAZ and TEAD

1. Juan F. Abenza
2. Leone Rossetti
3. Malèke Mouelhi
4. Javier Burgués
5. Ion Andreu
6. Keith Kennedy
7. Pere Roca-Cusachs
8. Santiago Marco
9. Jordi García-Ojalvo
10. Xavier Trepat

Reviewed by Review Commons

Composition can buffer protein dynamics within liquid-like condensates

1. Stela Jelenic
2. Janos Bindics
3. Philipp Czermak
4. Balashankar R Pillai
5. Martine Ruer
6. Carsten Hoege
7. Alex S Holehouse
8. Shambaditya Saha

Reviewed by Review Commons

Molecular basis for the role of disulfide-linked αCTs in the activation of insulin-like growth factor 1 receptor and insulin receptor

1. Jie Li
2. Jiayi Wu
3. Catherine Hall
4. Xiao-chen Bai
5. Eunhee Choi

• Curated by eLife

  Evaluation Summary:

  This is a valuable manuscript that addresses an important question and provides interesting mechanistic insights into the roles of specific regions of the IR and IGF1R in their activation. While many of the data convincingly support the conclusions, in some areas the data are incomplete so we are left with an unfinished picture of the mechanisms of activation of the IR and IGF1R, and why they differ.

  (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, Reviewer #2 and Reviewer #3 agreed to share their names with the authors.)

Reviewed by eLife

A sterol‐PI(4)P exchanger modulates the Tel1/ATM axis of the DNA damage response

1. Sara Ovejero
2. Sylvain Kumanski
3. Caroline Soulet
4. Julie Azarli
5. Benjamin Pardo
6. Olivier Santt
7. Angelos Constantinou
8. Philippe Pasero
9. María Moriel‐Carretero

Reviewed by Review Commons

Nanoscale structural organization and stoichiometry of the budding yeast kinetochore

1. Konstanty Cieslinski
2. Yu-Le Wu
3. Lisa Nechyporenko
4. Sarah Janice Hörner
5. Duccio Conti
6. Michal Skruzny
7. Jonas Ries

Reviewed by Review Commons

Connexin 43 hemichannels regulate mitochondrial ATP generation, mobilization, and mitochondrial homeostasis against oxidative stress

1. Jingruo Zhang
2. Manuel A Riquelme
3. Rui Hua
4. Francisca M Acosta
5. Sumin Gu
6. Jean X Jiang

• Curated by eLife

  Evaluation Summary:

  The manuscript is well organized and clearly written. The discussion provides the required information to easily understand the relevance of each finding. the authors demonstrated using an osteocyte cell model that connexin43 is localized to mitochondria and that this is enhanced in response to oxidative stress. Several lines of evidence were presented showing that mitochondrial connexin43 forms functional hemichannels and that connexin43 is required for optimal mitochondrial respiration and ATP generation. These aspects were major strengths of the study.

  (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 #3 agreed to share their name with the authors.)

Reviewed by eLife

Kinesin-1, -2, and -3 motors use family-specific mechanochemical strategies to effectively compete with dynein during bidirectional transport

1. Allison M Gicking
2. Tzu-Chen Ma
3. Qingzhou Feng
4. Rui Jiang
5. Somayesadat Badieyan
6. Michael A Cianfrocco
7. William O Hancock

• Curated by eLife

  Evaluation Summary:

  In their study, Gicking et al. study the physical properties of artificial complexes composed of the dynein-dynactin-BicD2 (DDB) complex linked to one of three classes of kinesins (1, 2, or 3) via a DNA scaffold. They find that all three kinesins can move to the plus-end of microtubules when coupled to the DDB complex. This is surprising because motors in the kinesin-2 and kinesin-3 families have been shown to have a higher load sensitivity. However, the authors show that the faster reattachment kinetics of these motors compensate for their faster detachment rates under load. This work is relevant to both the biophysics field for advancing knowledge in fundamental science, and in the neuroscience field since disruption of neuronal transport leads to a variety of neurodegenerative diseases.

  (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 #2 agreed to share their name with the authors.)

Reviewed by eLife