Table of Contents Alert: The EMBO Journal, Vol. 38, No. 9, 02 May 2019

The EMBO Journal Volume 38, Issue 9 02 May 2019

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Commentary

Open Access

A supporting ecosystem to mature extracellular vesicles into clinical application

Olivier De Wever, An Hendrix

e101412 | First Published: 12 April 2019

Research on Extracellular Vesicles (EV) holds great potential for developing diagnostic and therapeutic applications for a wide range of diseases. The authors define eight pillars and propose minimal guidelines for good laboratory practice and to improve experimental reproducibility and reliability in EV research.

News & Views

Lining up for quality control: linear ubiquitin and proteotoxicity

R Luke Wiseman

e101985 | First Published: 12 April 2019

While linear ubiquitin is well known to play a role in inflammatory signaling, new work shows that it is also regulates stability and proteotoxicity of protein aggregates involved in neurodegenerative diseases.

A choreography of intracellular Ca2+ and extracellular ATP to refine auditory nociceptors before hearing

Michael G Leitner, Dominik Oliver

e101980 | First Published: 12 April 2019

New work shows how coordinated Ca²⁺ waves in non‐sensory and sensory cells activate the nociception sensory system in the developing cochlea.

Articles

A protein quality control pathway regulated by linear ubiquitination

Eva M van Well, Verian Bader, Maria Patra, Ana Sánchez‐Vicente, Jens Meschede, Nikolas Furthmann, Cathrin Schnack, Alina Blusch, Joseph Longworth, Elisabeth Petrasch‐Parwez, Kohji Mori, Thomas Arzberger, Dietrich Trümbach, Lena Angersbach, Cathrin Showkat, Dominik A Sehr, Lena A Berlemann, Petra Goldmann, Albrecht M Clement, Christian Behl, Andreas C Woerner, Carsten Saft, Wolfgang Wurst, Christian Haass, Gisa Ellrichmann, Ralf Gold, Gunnar Dittmar, Mark S Hipp, F Ulrich Hartl, Jörg Tatzelt, Konstanze F Winklhofer

e100730 | First Published: 18 March 2019

Recruitment of the LUBAC E3 ligase, best known for its function in NF‐κB signalling, to protein aggregates for linear ubiquitin‐mediated removal of misfolded neurodegenerative disease proteins such as huntingtin, SOD1 or TDP‐43 exemplifies a new, potentially targetable cellular mechanism for controlling proteinopathies.

Open Access

Coordinated calcium signalling in cochlear sensory and non‐sensory cells refines afferent innervation of outer hair cells

Federico Ceriani, Aenea Hendry, Jing‐Yi Jeng, Stuart L Johnson, Friederike Stephani, Jennifer Olt, Matthew C Holley, Fabio Mammano, Jutta Engel, Corné J Kros, Dwayne D Simmons, Walter Marcotti

e99839 | First Published: 25 February 2019

Spontaneous Ca²⁺ waves in non‐sensory cells increase and synchronize Ca²⁺ signalling in outer hair cells via ATP‐induced activation of P2X₃ receptors, promoting functional differentiation and innervation of sensory cells.

Open Access

Mutant Lef1 controls Gata6 in sebaceous gland development and cancer

Bénédicte Oulès, Emanuel Rognoni, Esther Hoste, Georgina Goss, Ryan Fiehler, Ken Natsuga, Sven Quist, Remco Mentink, Giacomo Donati, Fiona M Watt

e100526 | First Published: 18 March 2019

Genetic work combined with lineage tracing analyses reveals a link between mutant Lef1 and Gata6 in the formation of sebaceous glands and associated tumors.

Open Access

A slow transcription rate causes embryonic lethality and perturbs kinetic coupling of neuronal genes

Magdalena M Maslon, Ulrich Braunschweig, Stuart Aitken, Abigail R Mann, Fiona Kilanowski, Chris J Hunter, Benjamin J Blencowe, Alberto R Kornblihtt, Ian R Adams, Javier F Cáceres

e101244 | First Published: 15 April 2019

RNA polymerase II elongation rates play key roles in expression and alternative splicing patterns of genes, with notably higher impact in neurons differentiating from embryonic stem cells than in pluripotent cells.

Open Access

TRAF6 directs FOXP3 localization and facilitates regulatory T‐cell function through K63‐linked ubiquitination

Xuhao Ni, Wei Kou, Jian Gu, Ping Wei, Xiao Wu, Hao Peng, Jinhui Tao, Wei Yan, Xiaoping Yang, Andriana Lebid, Benjamin V Park, Zuojia Chen, Yizhu Tian, Juan Fu, Stephanie Newman, Xiaoming Wang, Hongbin Shen, Bin Li, Bruce R. Blazar, Xuehao Wang, Joseph Barbi, Fan Pan, Ling Lu

e99766 | First Published: 18 March 2019

K63‐linked ubiquitination of FOXP3 by TRAF6 E3 ligase controls suppressive Treg functions, immune homeostasis and anti‐tumour immunity in mice.

Binding of IFT22 to the intraflagellar transport complex is essential for flagellum assembly

Stefanie Wachter, Jamin Jung, Shahaan Shafiq, Jerome Basquin, Cécile Fort, Philippe Bastin, Esben Lorentzen

e101251 | First Published: 02 April 2019

The X‐ray structures of IFT22/RabL5 reveal an unusual GTP/GDP‐binding mode and the structural basis for its interaction with the intraflagellar transport complex components IFT74/81 in regulation of flagellum formation in Trypanosoma.

Open Access

Intrinsic lipid binding activity of ATG16L1 supports efficient membrane anchoring and autophagy

Leo J Dudley, Ainara G Cabodevilla, Agata N Makar, Martin Sztacho, Tim Michelberger, Joseph A Marsh, Douglas R Houston, Sascha Martens, Xuejun Jiang, Noor Gammoh

e100554 | First Published: 01 April 2019

The core autophagy protein ATG16L1 binds phosphoinositides on pre‐autophagosomal structures via its coiled‐coil domain to promote LC3 lipidation and autophagosome maturation.

ALYREF links 3′‐end processing to nuclear export of non‐polyadenylated mRNAs

Jing Fan, Ke Wang, Xian Du, Jianshu Wang, Suli Chen, Yimin Wang, Min Shi, Li Zhang, Xudong Wu, Dinghai Zheng, Changshou Wang, Lantian Wang, Bin Tian, Guohui Li, Yu Zhou, Hong Cheng

e99910 | First Published: 12 March 2019

An RNA‐binding protein coupling nuclear export and 3′‐end processing of polyadenylated mRNAs exerts similar function on non‐polyadenylated replication‐dependent histone mRNAs.

Protein translocation by the SecA ATPase occurs by a power‐stroke mechanism

Marco A Catipovic, Benedikt W Bauer, Joseph J Loparo, Tom A Rapoport

e101140 | First Published: 15 March 2019

Single‐molecule FRET reveals that the bacterial SecA translocase uses ATP hydrolysis to push a polypeptide segment into the SecY channel, and phosphate release to slide it through the SecA‐SecY complex.

Corrigendum

The assembly of lipid droplets and their roles in challenged cells

W Mike Henne, Michael L Reese, Joel M Goodman

e101816 | First Published: 26 April 2019

This article is a correction.

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