Cell Biology

Efficiency and localisation of AURKA degradation by PROTACs is modulated by deubiquitinases UCHL5 and target-selective OTUD6A

1. Annabel Cardno
2. Karen Roberts
3. Catherine Lindon

• Curated by eLife

  eLife Assessment

  This study describes a genetic screen to identify deubiquitinases (DUBs) that counteract the activity of small-molecule degraders (PROTACs). The presented data are valuable, identifying OTUD6A and UCHL5 as DUBs that impact the efficacy and potency of PROTACs. While the conclusions are broadly supported and the methods employed are solid, the mechanistic depth and validation are incomplete. Overall, these findings merit further evaluation by the targeted protein degradation community when developing and optimizing PROTACs.

Reviewed by eLife

The insulin / IGF axis is critically important controlling gene transcription in the podocyte

1. Jennifer A Hurcombe
2. Lusyan Dayalan
3. Fern Barrington
4. Frédéric Burdet
5. Lan Ni
6. Joseph T Coward
7. Paul T Brinkkoetter
8. Martin Holzenberger
9. Aaron Jeffries
10. Sebastian Oltean
11. Gavin I Welsh
12. Richard JM Coward

• Curated by eLife

  eLife Assessment

  This study investigated the role of insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) in the renal glomerular podocytes by characterizing the mice with dual deletion of both receptors in vivo as well as the cultured murine podocytes with induced deletion of both receptors in vitro. The solid data presented in this paper demonstrated the critical requirement of both IR and IGF1R signaling in normal podocyte physiology in mice, albeit a more detailed characterization of the mouse model is desired. Interestingly, long-range sequencing revealed significant retention of introns in mRNAs, due to an altered spliceosome level resulted from the loss of IR and IGF1 signaling in cultured podocytes. This new finding suggests an essential role of IR and IGF1R signaling in regulating RNA metabolism in podocyte, which provides useful information for the understanding of physiology and metabolism of podocytes. However, the underlying molecular mechanism for such a regulation is still unclear and awaits further studies.

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

Reviewed by eLife

A biochemical mechanism for Stu2/XMAP215-family microtubule polymerases

1. Binnu Gangadharan
2. Daniel L Kober
3. Luke M Rice

• Curated by eLife

  eLife Assessment

  In their important manuscript, Gangadharan, Kober and Rice focus on how Stu2/XMAP215-family microtubule polymerases use their TOG domains to catalytically promote microtubule growth, testing whether their mechanism follows an enzyme-like kinetic model similar to that of actin polymerases. The authors integrate measurements including microtubule polymerization rates and TOG-tubulin binding kinetics to convincingly show that Stu2 follows an enzyme-like model where tight tubulin binding enables efficient polymerization, revealing a shared mechanism with actin polymerases despite their evolutionary divergence. This work will be of general interest to the cell biology and biophysics communities.

Reviewed by eLife

Fertilization triggers cytosolic functions and P-body recruitment of the RNA-binding protein Mei2 to drive fission yeast zygotic development

1. Ayokunle Araoyinbo
2. Clàudia Salat-Canela
3. Aleksandar Vještica

Reviewed by Review Commons

Optogenetic control of mechanotransduction based on light-induced homodimerization of talin

1. Ryosuke Nishimura
2. Samuel F. H. Barnett
3. Kashish Jain
4. Zengxin Huang
5. Benjamin T. Goult
6. Pakorn Kanchanawong

Reviewed by preLights

Transcriptional dynamics uncover the role of BNIP3 in mitophagy during muscle remodeling in Drosophila

1. Hiroki Taoka
2. Tadayoshi Murakawa
3. Kohei Kawaguchi
4. Michiko Koizumi
5. Tatsuya Kaminishi
6. Yuriko Sakamaki
7. Kaori Tanaka
8. Akihito Harada
9. Keiichi Inoue
10. Tomotake Kanki
11. Yasuyuki Ohkawa
12. Naonobu Fujita

• Curated by eLife

  eLife Assessment

  This paper presents the important finding that BNIP3/NIX, a mitophagy receptor, and its binding to ATG18 are required for mitophagy during muscle cell reorganization in Drosophila. Although the involvement of the BNIP3-ATG18/WIPI axis in mitophagy induction has been reported in mammalian cell culture systems, this study provides the first compelling evidence for this pathway in vivo in animals. The physiological significance of this BNIP3-dependent mitophagy will require further investigation.

Reviewed by eLife

ATG2A engages RAB1A and ARFGAP1 positive membranes during autophagosome biogenesis

1. Devin M Fuller
2. Yumei Wu
3. Florian Schueder
4. Burha Rasool
5. Shanta Nag
6. Justin L Korfhage
7. Rolando Garcia-Milian
8. Katerina D Melnyk
9. Joerg Bewersdorf
10. Pietro De Camilli
11. Thomas J Melia

• Curated by eLife

  eLife Assessment

  This study provides valuable insights into the crosstalk between ATG2A with components of the early secretory pathway, namely RAB1A and ARFGAP1. The evidence supporting the claims is convincing. However, the manuscript would benefit from a more in-depth exploration of the details of the role of RAB1A in autophagy and the functional implications of its interaction with ATG2A. In addition, the molecular details of the role of ARFGAP1 in this complex need further clarification

Reviewed by eLife

Live-cell imaging reveals nutrient-dependent dynamics of ER-mitochondria contact formation via PDZD8

1. Saeko Aoyama-Ishiwatari
2. Koki Nakamura
3. Takahiro Nagao
4. Yusuke Hirabayashi

Reviewed by Review Commons

G1 and G2 ApolipoproteinL1 modulate macrophage inflammation and lipid accumulation through the polyamine pathway

1. Esther Liu
2. Matthew Wright
3. Andrew O Kearney
4. Tiffany Caza
5. Johnson Y Yang
6. Valerie Garcia
7. Amal O Dadi
8. Shuta Ishibe
9. Navdeep S Chandel
10. Hanrui Zhang
11. Edward B Thorp
12. Jennie Lin

• Curated by eLife

  eLife Assessment

  The authors study how apolipoprotein L1 variants impact inflammation and lipid accumulation in macrophages. The findings will be useful for researchers investigating macrophage metabolism and inflammation. The discovery that the polyamine spermidine in part mediates such effects is interesting, but the supporting evidence for a physiologically relevant role is currently incomplete due to the lack of relevant in vivo studies.

Reviewed by eLife

Impact of maximal overexpression of a non-toxic protein on yeast cell physiology

1. Yuri Fujita
2. Shotaro Namba
3. Yoshiaki Kamada
4. Hisao Moriya

• Curated by eLife

  eLife assessment

  This convincing study advances our understanding of the physiological consequences of the strong overexpression of non-toxic proteins in baker's yeast. The findings suggest that a massive protein burden results in nitrogen starvation and a shift in metabolism likely regulated via the TORC1 pathway, as well as defects in ribosome biogenesis in the nucleolus. The study presents findings and tools that are important for the cell biology and protein homeostasis fields.

Reviewed by eLife