EMBO reports Volume 20, Issue 10 04 October 2019 |
News & Views
A snapshot of membrane protein insertion
EMBO Rep (2019) 20: e49034 | First Published: 13 September 2019
The SecYEG translocon provides the major route for co‐translational membrane protein insertion in bacteria. A cryo‐electron microscopy structure of SecYEG in lipid nanodiscs bound to a translating ribosome reveals an intermediate stage of protein insertion.
The ubiquitin E2 enzyme UBE2QL1 mediates lysophagy
EMBO Rep (2019) 20: e49104 | First Published: 15 September 2019
The autophagic clearance of damaged lysosomes with ruptured membranes involves their extensive ubiquitination. A study in this issue identifies the E2 enzyme UBE2QL1 as an important player in lysophagy and lysosomal homeostasis.
Science & Society
The limits of machine intelligence : Despite progress in machine intelligence, artificial general intelligence is still a major challenge
EMBO Rep (2019) 20: e49177 | First Published: 18 September 2019
Despite recent breakthroughs in machine learning, current artificial systems lack key features of biological intelligence. Whether the current limitations can be overcome is an open question, but critical to answer, given the implications for society.
Preparing biomedical students for the unknown : Some unusual challenges for students to help them understand the fundamentals of empirical research
EMBO Rep (2019) 20: e49004 | First Published: 15 September 2019
Make teaching challenging again: a pedagogic approach to educate students on how to do science rather than learn about it.
Why control an experiment? : From empiricism, via consciousness, toward Implicate Order
EMBO Rep (2019) 20: e49110 | First Published: 03 September 2019
Empirical research is based on observation and experimentation. Yet, experimental controls are essential for overcoming our sensory limits and generating reliable, unbiased and objective results.
Illuminating human disease : The potential of in vivo imaging for preclinical research and diagnostics
EMBO Rep (2019) 20: e49195 | First Published: 16 September 2019
New in vivo imaging technologies, including optical methods to observe biological processes in real time, show great promise for preclinical research and diagnostics of human diseases.
Review
Mitochondria orchestrate proteostatic and metabolic stress responses
EMBO Rep (2019) 20: e47865 | First Published: 18 September 2019
The eukaryotic cell consists of an interconnected network of organelles that need to communicate and orchestrate their response to cellular stresses and aging. This review discusses the regulatory pathways that sense and control metabolism and sub‐cellular proteostasis systems with a focus on mitochondria‐to‐nucleus signaling.
Reports
Partially inserted nascent chain unzips the lateral gate of the Sec translocon
EMBO Rep (2019) 20: e48191 | First Published: 05 August 2019
Cryo‐electron microscopy and atomistic simulations of SecYEG in the lipid environment reveal an early stage of membrane protein insertion. The flexible nascent chain triggers a conformational change that pre‐opens the translocon.
PPM1G forms a PPP‐type phosphatase holoenzyme with B56δ that maintains adherens junction integrity
EMBO Rep (2019) 20: e46965 | First Published: 21 August 2019
PPM family phosphatases are thought to act as monomers. This study shows that PPM1G forms a distinct holoenzyme complex with the PP2A regulatory subunit B56δ in the cytoplasm that functions in adherens junction assembly.
Diflunisal targets the HMGB1/CXCL12 heterocomplex and blocks immune cell recruitment
EMBO Rep (2019) 20: e47788 | First Published: 14 August 2019
Diflunisal, which is a drug in use in the clinic, selectively inhibits the chemotactic activity of HMGB1/CXCL12 complex.
Pannexin‐1 limits the production of proinflammatory cytokines during necroptosis
EMBO Rep (2019) 20: e47840 | First Published: 14 August 2019
The activation of MLKL by RIPK3 controls the execution of necroptosis. During the early stages of necroptotic cell death, MLKL oligomers promote the activation of Pannexin‐1 channels, which constricts the production of proinflammatory cytokines.
CDK12 drives breast tumor initiation and trastuzumab resistance via WNT and IRS1‐ErbB‐PI3K signaling
EMBO Rep (2019) 20: e48058 | First Published: 30 August 2019
CDK12, a RNA polymerase II kinase, promotes breast cancer stem cell‐like properties mediated by WNT and ErbB‐PI3K signaling. Targeting CDK12 improves trastuzumab therapy in breast cancers characterised by HER2/CDK12 co‐amplification.
Articles
The ubiquitin‐conjugating enzyme UBE2QL1 coordinates lysophagy in response to endolysosomal damage
EMBO Rep (2019) 20: e48014 | First Published: 21 August 2019
Lysophagy, the selective autophagy of permeabilized lysosomes, requires extensive ubiquitination of the damaged organelle. The ubiquitin‐conjugating enzyme UBE2QL1 is a key coordinator of lysosome ubiquitination and lysophagy after lysosomal damage.
Targeting of early endosomes by autophagy facilitates EGFR recycling and signalling
EMBO Rep (2019) 20: e47734 | First Published: 26 August 2019
Targeting of damaged organelles by autophagy is crucial for cell homeostasis. This study identifies a novel function of the autophagy machinery in recognising damaged early endosomes, the absence of which compromises EGFR trafficking and signalling.
Dysregulation of cystathionine γ‐lyase promotes prostate cancer progression and metastasis
EMBO Rep (2019) 20: e45986 | First Published: 29 August 2019
Cystathionine‐γ‐lyase (CTH) and its catalyzed product hydrogen sulfide, a known gaseous transmitter, are dysregulated in prostate cancer. Increased CTH activity promotes cancer progression and metastasis via the sulfhydration of the NF‐κB subunit p65.
S‐acylated Golga7b stabilises DHHC5 at the plasma membrane to regulate cell adhesion
EMBO Rep (2019) 20: e47472 | First Published: 12 August 2019
Cell membrane localized DHHC5 palmitoylates components of desmosomes and promotes cell adhesion.
TDP2 negatively regulates axon regeneration by inducing SUMOylation of an Ets transcription factor
EMBO Rep (2019) 20: e47517 | First Published: 08 August 2019
The Mxl‐1 transcription factor promotes axon regeneration in C. elegans via inhibition of TDPT‐1, which reduces ETS‐4 SUMOylation and increases svh‐2 transcription.
Rab35 controls cilium length, function and membrane composition
EMBO Rep (2019) 20: e47625 | First Published: 21 August 2019
Rab35 at the mammalian and zebrafish cilium regulates cilium length and left‐right asymmetry, and controls the ciliary levels of PI(4,5)P2 and regulators of the Sonic hedgehog pathway.
Trehalose‐6‐phosphate signaling regulates thermoresponsive hypocotyl growth in Arabidopsis thaliana
EMBO Rep (2019) 20: e47828 | First Published: 08 August 2019
Trehalose‐6‐phosphate is a signaling molecule coordinating endogenous sugar availability and plant growth at high temperatures.
Robotic platform for microinjection into single cells in brain tissue
EMBO Rep (2019) 20: e47880 | First Published: 30 August 2019
This study reports the Autoinjector, a robotic tool that enables microinjection of hundreds of cells within a single organotypic slice. The robot is validated in brain tissues and renders microinjection a broadly accessible high‐performance cell manipulation technique.
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