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Lenka Belicova, Urska Repnik, Julien Delpierre, Elzbieta Gralinska, Sarah Seifert, José Ignacio Valenzuela, Hernán Morales-Navarrete, Christian Franke, Helin Räägel, Evgeniya Shcherbinina, Tatiana Prikazchikova, Victor Koteliansky, Martin Vingron, Yannis Kalaidzidis, Timofei Zatsepin, Marino Zerial
Anisotropic expansion of hepatocyte lumina enforced by apical bulkheads.
J Cell Biol, 220(10) Art. No. e202103003 (2021)
Open Access PubMed Source   

Lumen morphogenesis results from the interplay between molecular pathways and mechanical forces. In several organs, epithelial cells share their apical surfaces to form a tubular lumen. In the liver, however, hepatocytes share the apical surface only between adjacent cells and form narrow lumina that grow anisotropically, generating a 3D network of bile canaliculi (BC). Here, by studying lumenogenesis in differentiating mouse hepatoblasts in vitro, we discovered that adjacent hepatocytes assemble a pattern of specific extensions of the apical membrane traversing the lumen and ensuring its anisotropic expansion. These previously unrecognized structures form a pattern, reminiscent of the bulkheads of boats, also present in the developing and adult liver. Silencing of Rab35 resulted in loss of apical bulkheads and lumen anisotropy, leading to cyst formation. Strikingly, we could reengineer hepatocyte polarity in embryonic liver tissue, converting BC into epithelial tubes. Our results suggest that apical bulkheads are cell-intrinsic anisotropic mechanical elements that determine the elongation of BC during liver tissue morphogenesis.
@article{Belicova8123,
author={Lenka Belicova, Urska Repnik, Julien Delpierre, Elzbieta Gralinska, Sarah Seifert, José Ignacio Valenzuela, Hernán Morales-Navarrete, Christian Franke, Helin Räägel, Evgeniya Shcherbinina, Tatiana Prikazchikova, Victor Koteliansky, Martin Vingron, Yannis Kalaidzidis, Timofei Zatsepin, Marino Zerial},
title={Anisotropic expansion of hepatocyte lumina enforced by apical bulkheads.},
journal ={The Journal of cell biology},
volume={220},
issue ={10},
pages={null--null},
year=2021
}

Glyn Nelson✳︎#, Ulrike Boehm✳︎#, Steve Bagley, Peter Bajcsy, Johanna Bischof, Claire M Brown, Aurélien Dauphin, Ian M Dobbie, John E Eriksson, Orestis Faklaris, Julia Fernandez-Rodriguez, Alexia Ferrand, Laurent Gelman, Ali Gheisari, Hella Hartmann, Christian Kukat, Alex Laude, Miso Mitkovski, Sebastian Munck, Alison J North, Tobias Manuel Rasse, Ute Resch-Genger, Lucas C Schuetz, Arne Seitz, Caterina Strambio-De-Castillia, Jason R Swedlow, Ioannis Alexopoulos, Karin Aumayr, Sergiy Avilov, Gert-Jan Bakker, Rodrigo R Bammann, Andrea Bassi, Hannes Beckert, Sebastian Beer, Yury Belyaev, Jakob Bierwagen, Konstantin A Birngruber, Manel Bosch, Juergen Breitlow, Lisa A Cameron, Joe Chalfoun, James J Chambers, Chieh-Li Chen, Eduardo Conde-Sousa, Alexander D Corbett, Fabrice P Cordelieres, Elaine Del Nery, Ralf Dietzel, Frank Eismann, Elnaz Fazeli, Andreas Felscher, Hans-Ulrich Fried, Nathalie Gaudreault, Wah Ing Goh, Thomas Guilbert, Roland Hadleigh, Peter Hemmerich, Gerhard A Holst, Michelle S Itano, Claudia B Jaffe, Helena Jambor, Stuart C Jarvis, Antje Keppler, David Kirchenbuechler, Marcel Kirchner, Norio Kobayashi, Gabriel Krens, Susanne Kunis, Judith Lacoste, Maresca Marcello, Gabriel G Martins, Daniel J Metcalf, Claire A Mitchell, Joshua Moore, Tobias Mueller, Michael S Nelson, Stephen Ogg, Shuichi Onami, Alexandra L Palmer, Perrine Paul-Gilloteaux, Jaime A Pimentel, Laure Plantard, Santosh Podder, Elton Rexhepaj, Arnaud Royon, Markku A Saari, Damien Schapman, Vincent Schoonderwoert, Britta Schroth-Diez, Stanley Schwartz, Michael Shaw, Martin Spitaler, Martin T Stoeckl, Damir Sudar, Jeremie Teillon, Stefan Terjung, Roland Thuenauer, Christian D Wilms, Graham D Wright, Roland Nitschke#
QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy.
J Microsc, 284(1) 56-73 (2021)
Open Access PubMed Source   

A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics.
@article{Nelson8102,
author={Glyn Nelson, Ulrike Boehm, Steve Bagley, Peter Bajcsy, Johanna Bischof, Claire M Brown, Aurélien Dauphin, Ian M Dobbie, John E Eriksson, Orestis Faklaris, Julia Fernandez-Rodriguez, Alexia Ferrand, Laurent Gelman, Ali Gheisari, Hella Hartmann, Christian Kukat, Alex Laude, Miso Mitkovski, Sebastian Munck, Alison J North, Tobias Manuel Rasse, Ute Resch-Genger, Lucas C Schuetz, Arne Seitz, Caterina Strambio-De-Castillia, Jason R Swedlow, Ioannis Alexopoulos, Karin Aumayr, Sergiy Avilov, Gert-Jan Bakker, Rodrigo R Bammann, Andrea Bassi, Hannes Beckert, Sebastian Beer, Yury Belyaev, Jakob Bierwagen, Konstantin A Birngruber, Manel Bosch, Juergen Breitlow, Lisa A Cameron, Joe Chalfoun, James J Chambers, Chieh-Li Chen, Eduardo Conde-Sousa, Alexander D Corbett, Fabrice P Cordelieres, Elaine Del Nery, Ralf Dietzel, Frank Eismann, Elnaz Fazeli, Andreas Felscher, Hans-Ulrich Fried, Nathalie Gaudreault, Wah Ing Goh, Thomas Guilbert, Roland Hadleigh, Peter Hemmerich, Gerhard A Holst, Michelle S Itano, Claudia B Jaffe, Helena Jambor, Stuart C Jarvis, Antje Keppler, David Kirchenbuechler, Marcel Kirchner, Norio Kobayashi, Gabriel Krens, Susanne Kunis, Judith Lacoste, Maresca Marcello, Gabriel G Martins, Daniel J Metcalf, Claire A Mitchell, Joshua Moore, Tobias Mueller, Michael S Nelson, Stephen Ogg, Shuichi Onami, Alexandra L Palmer, Perrine Paul-Gilloteaux, Jaime A Pimentel, Laure Plantard, Santosh Podder, Elton Rexhepaj, Arnaud Royon, Markku A Saari, Damien Schapman, Vincent Schoonderwoert, Britta Schroth-Diez, Stanley Schwartz, Michael Shaw, Martin Spitaler, Martin T Stoeckl, Damir Sudar, Jeremie Teillon, Stefan Terjung, Roland Thuenauer, Christian D Wilms, Graham D Wright, Roland Nitschke},
title={QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy.},
journal ={Journal of microscopy},
volume={284},
issue ={1},
pages={56--73},
year=2021
}

Cemil Kerimoglu✳︎, Linh Pham✳︎, Anton B Tonchev✳︎, M Sadman Sakib✳︎, Yuanbin Xie, Godwin Sokpor, Pauline Antonie Ulmke, Lalit Kaurani, Eman Abbas, Huong Nguyen, Joachim Rosenbusch, Alexandra Michurina, Vincenzo Capece, Meglena Angelova, Nenad Maricic, Beate Brand-Saberi, Miriam Esgleas, Mareike Albert, Radoslav Minkov, Emil Kovachev, Ulrike Teichmann, Rho H Seong, Wieland Huttner, Huu Phuc Nguyen, Anastassia Stoykova, Jochen F Staiger, Andre Fischer#, Tran Tuoc#
H3 acetylation selectively promotes basal progenitor proliferation and neocortex expansion.
Sci Adv, 7(38) Art. No. eabc6792 (2021)
Open Access PubMed Source   

Increase in the size of human neocortex―acquired in evolution―accounts for the unique cognitive capacity of humans. This expansion reflects the evolutionarily enhanced proliferative ability of basal progenitors (BPs), including the basal radial glia and basal intermediate progenitors (bIPs) in mammalian cortex, which may have been acquired through epigenetic alterations in BPs. However, how the epigenome in BPs differs across species is not known. Here, we report that histone H3 acetylation is a key epigenetic regulation in bIP amplification and cortical expansion. Through epigenetic profiling of sorted bIPs, we show that histone H3 lysine 9 acetylation (H3K9ac) is low in murine bIPs and high in human bIPs. Elevated H3K9ac preferentially increases bIP proliferation, increasing the size and folding of the normally smooth mouse neocortex. H3K9ac drives bIP amplification by increasing expression of the evolutionarily regulated gene, Trnp1, in developing cortex. Our findings demonstrate a previously unknown mechanism that controls cortical architecture.
@article{Kerimoglu8182,
author={Cemil Kerimoglu, Linh Pham, Anton B Tonchev, M Sadman Sakib, Yuanbin Xie, Godwin Sokpor, Pauline Antonie Ulmke, Lalit Kaurani, Eman Abbas, Huong Nguyen, Joachim Rosenbusch, Alexandra Michurina, Vincenzo Capece, Meglena Angelova, Nenad Maricic, Beate Brand-Saberi, Miriam Esgleas, Mareike Albert, Radoslav Minkov, Emil Kovachev, Ulrike Teichmann, Rho H Seong, Wieland Huttner, Huu Phuc Nguyen, Anastassia Stoykova, Jochen F Staiger, Andre Fischer, Tran Tuoc},
title={H3 acetylation selectively promotes basal progenitor proliferation and neocortex expansion.},
journal ={Science advances},
volume={7},
issue ={38},
pages={null--null},
year=2021
}

Anatol Fritsch✳︎, Andrés F Diaz-Delgadillo✳︎, Omar Adame-Arana✳︎, Carsten Hoege, Matthäus Mittasch, Moritz Kreysing, Mark Leaver, Anthony Hyman, Frank Jülicher, Christoph A. Weber
Local thermodynamics govern formation and dissolution of Caenorhabditis elegans P granule condensates.
Proc Natl Acad Sci U.S.A., 118(37) Art. No. e2102772118 (2021)
PubMed Source   

Membraneless compartments, also known as condensates, provide chemically distinct environments and thus spatially organize the cell. A well-studied example of condensates is P granules in the roundworm Caenorhabditis elegans that play an important role in the development of the germline. P granules are RNA-rich protein condensates that share the key properties of liquid droplets such as a spherical shape, the ability to fuse, and fast diffusion of their molecular components. An outstanding question is to what extent phase separation at thermodynamic equilibrium is appropriate to describe the formation of condensates in an active cellular environment. To address this question, we investigate the response of P granule condensates in living cells to temperature changes. We observe that P granules dissolve upon increasing the temperature and recondense upon lowering the temperature in a reversible manner. Strikingly, this temperature response can be captured by in vivo phase diagrams that are well described by a Flory-Huggins model at thermodynamic equilibrium. This finding is surprising due to active processes in a living cell. To address the impact of such active processes on intracellular phase separation, we discuss temperature heterogeneities. We show that, for typical estimates of the density of active processes, temperature represents a well-defined variable and that mesoscopic volume elements are at local thermodynamic equilibrium. Our findings provide strong evidence that P granule assembly and disassembly are governed by phase separation based on local thermal equilibria where the nonequilibrium nature of the cytoplasm is manifested on larger scales.
@article{Fritsch8178,
author={Anatol Fritsch, Andrés F Diaz-Delgadillo, Omar Adame-Arana, Carsten Hoege, Matthäus Mittasch, Moritz Kreysing, Mark Leaver, Anthony Hyman, Frank Jülicher, Christoph A. Weber},
title={Local thermodynamics govern formation and dissolution of Caenorhabditis elegans P granule condensates.},
journal ={Proceedings of the National Academy of Sciences of the United States of America},
volume={118},
issue ={37},
pages={null--null},
year=2021
}

Elisabeth Kemter✳︎, Andreas Müller✳︎, Martin Neukam, Anna Ivanova, Nikolai Klymiuk, Simone Renner, Kaiyuan Yang, Johannes Broichhagen, Mayuko Kurome, Valeri Zakhartchenko, Barbara Kessler, Klaus-Peter Knoch, Marc Bickle, Barbara Ludwig, Kai Johnsson, Heiko Lickert, Thomas Kurth, Eckhard Wolf✳︎#, Michele Solimena✳︎#
Sequential in vivo labeling of insulin secretory granule pools in INS-SNAP transgenic pigs.
Proc Natl Acad Sci U.S.A., 118(37) Art. No. e2107665118 (2021)
Open Access PubMed Source   

β cells produce, store, and secrete insulin upon elevated blood glucose levels. Insulin secretion is a highly regulated process. The probability for insulin secretory granules to undergo fusion with the plasma membrane or being degraded is correlated with their age. However, the molecular features and stimuli connected to this behavior have not yet been fully understood. Furthermore, our understanding of β cell function is mostly derived from studies of ex vivo isolated islets in rodent models. To overcome this translational gap and study insulin secretory granule turnover in vivo, we have generated a transgenic pig model with the SNAP-tag fused to insulin. We demonstrate the correct targeting and processing of the tagged insulin and normal glycemic control of the pig model. Furthermore, we show specific single- and dual-color granular labeling of in vivo-labeled pig pancreas. This model may provide unprecedented insights into the in vivo insulin secretory granule behavior in an animal close to humans.
@article{Kemter8180,
author={Elisabeth Kemter, Andreas Müller, Martin Neukam, Anna Ivanova, Nikolai Klymiuk, Simone Renner, Kaiyuan Yang, Johannes Broichhagen, Mayuko Kurome, Valeri Zakhartchenko, Barbara Kessler, Klaus-Peter Knoch, Marc Bickle, Barbara Ludwig, Kai Johnsson, Heiko Lickert, Thomas Kurth, Eckhard Wolf, Michele Solimena},
title={Sequential in vivo labeling of insulin secretory granule pools in INS-SNAP transgenic pigs.},
journal ={Proceedings of the National Academy of Sciences of the United States of America},
volume={118},
issue ={37},
pages={null--null},
year=2021
}

Hsiu-Chuan Lin✳︎, Zhisong He✳︎, Sebastian Ebert✳︎, Maria Schörnig, Malgorzata Santel, Marina T Nikolova, Anne Weigert, Wulf Hevers, Nael Nadif Kasri, Elena Taverna, J Gray Camp#, Barbara Treutlein#
NGN2 induces diverse neuron types from human pluripotency.
Stem Cell Reports, 16(9) 2118-2127 (2021)
Open Access PubMed Source   

Human neurons engineered from induced pluripotent stem cells (iPSCs) through neurogenin 2 (NGN2) overexpression are widely used to study neuronal differentiation mechanisms and to model neurological diseases. However, the differentiation paths and heterogeneity of emerged neurons have not been fully explored. Here, we used single-cell transcriptomics to dissect the cell states that emerge during NGN2 overexpression across a time course from pluripotency to neuron functional maturation. We find a substantial molecular heterogeneity in the neuron types generated, with at least two populations that express genes associated with neurons of the peripheral nervous system. Neuron heterogeneity is observed across multiple iPSC clones and lines from different individuals. We find that neuron fate acquisition is sensitive to NGN2 expression level and the duration of NGN2-forced expression. Our data reveal that NGN2 dosage can regulate neuron fate acquisition, and that NGN2-iN heterogeneity can confound results that are sensitive to neuron type.
@article{Lin8129,
author={Hsiu-Chuan Lin, Zhisong He, Sebastian Ebert, Maria Schörnig, Malgorzata Santel, Marina T Nikolova, Anne Weigert, Wulf Hevers, Nael Nadif Kasri, Elena Taverna, J Gray Camp, Barbara Treutlein},
title={NGN2 induces diverse neuron types from human pluripotency.},
journal ={Stem cell reports},
volume={16},
issue ={9},
pages={2118--2127},
year=2021
}

Pallavi Subramanian✳︎#, Sofia Gargani✳︎, Alessandra Palladini, Margarita Chatzimike, Michal Grzybek, M Peitzsch, Anastasios D Papanastasiou, Iryna Pyrina, Vasileios Ntafis, Bettina Gercken, Mathias Lesche, Andreas Petzold, Anupam Sinha, Marina Nati, Veera Raghavan Thangapandi, Ioannis Kourtzelis, Margarita Andreadou, Anke Witt, Andreas Dahl, Ralph Burkhardt, Robert Haase, Antonio Domingues, Ian Henry, Nicola Zamboni, Peter Mirtschink, Kyoung-Jin Chung, Jochen Hampe, Ünal Coskun, Dimitris L Kontoyiannis#, Trian Chavakis#
The RNA binding protein HuR is a gatekeeper of liver homeostasis.
Hepatology, Art. No. 10.1002/hep.32153 (2021)
PubMed Source   

Non-alcoholic fatty liver disease (NAFLD) is initiated by steatosis and can progress via fibrosis and cirrhosis to hepatocellular carcinoma (HCC). The RNA binding protein HuR controls RNAs at the posttranscriptional level; hepatocyte HuR has been implicated in the regulation of diet-induced hepatic steatosis. The present study aimed to understand the role of hepatocyte-HuR in NAFLD development and progression to fibrosis and HCC.
@article{Subramanian8181,
author={Pallavi Subramanian, Sofia Gargani, Alessandra Palladini, Margarita Chatzimike, Michal Grzybek, M Peitzsch, Anastasios D Papanastasiou, Iryna Pyrina, Vasileios Ntafis, Bettina Gercken, Mathias Lesche, Andreas Petzold, Anupam Sinha, Marina Nati, Veera Raghavan Thangapandi, Ioannis Kourtzelis, Margarita Andreadou, Anke Witt, Andreas Dahl, Ralph Burkhardt, Robert Haase, Antonio Domingues, Ian Henry, Nicola Zamboni, Peter Mirtschink, Kyoung-Jin Chung, Jochen Hampe, Ünal Coskun, Dimitris L Kontoyiannis, Trian Chavakis},
title={The RNA binding protein HuR is a gatekeeper of liver homeostasis.},
journal ={Hepatology (Baltimore, Md.)},
volume={},
pages={null--null},
year=2021
}

Stefano Suzzi, Reiner Ahrendt, Stefan Hans, Svetlana A Semenova, Avinash Chekuru, Paul Wirsching, Volker Kroehne, Saygın Bilican, Shady Sayed, Sylke Winkler, Sandra Spieß, Anja Machate, Jan Kaslin, Pertti Panula, Michael Brand
Deletion of lrrk2 causes early developmental abnormalities and age-dependent increase of monoamine catabolism in the zebrafish brain.
PLoS Genet, 17(9) Art. No. 1009794 (2021)
Open Access PubMed Source   

LRRK2 gain-of-function is considered a major cause of Parkinson's disease (PD) in humans. However, pathogenicity of LRRK2 loss-of-function in animal models is controversial. Here we show that deletion of the entire zebrafish lrrk2 locus elicits a pleomorphic transient brain phenotype in maternal-zygotic mutant embryos (mzLrrk2). In contrast to lrrk2, the paralog gene lrrk1 is virtually not expressed in the brain of both wild-type and mzLrrk2 fish at different developmental stages. Notably, we found reduced catecholaminergic neurons, the main target of PD, in specific cell populations in the brains of mzLrrk2 larvae, but not adult fish. Strikingly, age-dependent accumulation of monoamine oxidase (MAO)-dependent catabolic signatures within mzLrrk2 brains revealed a previously undescribed interaction between LRRK2 and MAO biological activities. Our results highlight mzLrrk2 zebrafish as a tractable tool to study LRRK2 loss-of-function in vivo, and suggest a link between LRRK2 and MAO, potentially of relevance in the prodromic stages of PD.
@article{Suzzi8183,
author={Stefano Suzzi, Reiner Ahrendt, Stefan Hans, Svetlana A Semenova, Avinash Chekuru, Paul Wirsching, Volker Kroehne, Saygın Bilican, Shady Sayed, Sylke Winkler, Sandra Spieß, Anja Machate, Jan Kaslin, Pertti Panula, Michael Brand},
title={Deletion of lrrk2 causes early developmental abnormalities and age-dependent increase of monoamine catabolism in the zebrafish brain.},
journal ={PLoS genetics},
volume={17},
issue ={9},
pages={null--null},
year=2021
}

Florian Peters✳︎, Sascha Rahn✳︎, Marion Mengel, Franka Scharfenberg, Anna Otte, Tomas Koudelka, Erwin F Wagner, F Thomas Wunderlich, Michael Haase, Ronald Naumann, Andreas Tholey, Christoph Becker-Pauly
Syndecan-1 shedding by meprin β impairs keratinocyte adhesion and differentiation in hyperkeratosis.
Matrix Biol, Art. No. 10.1016/j.matbio.2021.08.002 (2021)
PubMed Source   

Dysregulation of proteolytic enzymes has huge impact on epidermal homeostasis, which can result in severe pathological conditions such as fibrosis or Netherton syndrome. The metalloprotease meprin β was found to be upregulated in hyperproliferative skin diseases. AP-1 transcription factor complex has been reported to induce Mep1b expression. Since AP-1 and its subunit fos-related antigen 2 (fra-2) are associated with the onset and progression of psoriasis, we wanted to investigate if this could partially be attributed to increased meprin β activity. Here, we demonstrate that fra-2 transgenic mice show increased meprin β expression and proteolytic activity in the epidermis. To avoid influence by other fra-2 regulated genes, we additionally generated a mouse model that enabled tamoxifen-inducible expression of meprin β under the Krt5-promotor to mimic the pathological condition. Interestingly, induced meprin β expression in the epidermis resulted in hyperkeratosis, hair loss and mottled pigmentation of the skin. Employing N-terminomics revealed syndecan-1 as a substrate of meprin β in skin. Shedding of syndecan-1 at the cell surface caused delayed calcium-induced differentiation and impaired adhesion of keratinocytes, which was blocked by the meprin β inhibitor fetuin-B.
@article{Peters8177,
author={Florian Peters, Sascha Rahn, Marion Mengel, Franka Scharfenberg, Anna Otte, Tomas Koudelka, Erwin F Wagner, F Thomas Wunderlich, Michael Haase, Ronald Naumann, Andreas Tholey, Christoph Becker-Pauly},
title={Syndecan-1 shedding by meprin β impairs keratinocyte adhesion and differentiation in hyperkeratosis.},
journal ={Matrix biology : journal of the International Society for Matrix Biology},
volume={},
pages={null--null},
year=2021
}

Edgar Boczek✳︎, Julius Fürsch✳︎, Marie Laura Niedermeier, Louise Jawerth, Marcus Jahnel, Martine Ruer-Gruß, Kai-Michael Kammer, Paul J Heid, Laura Mediani, Jie Wang, Xiao Yan, Andrei Pozniakovski, Ina Poser, Daniel Mateju, Lars Hubatsch, Serena Carra, Dr Simon Alberti, Anthony Hyman, Florian Stengel
HspB8 prevents aberrant phase transitions of FUS by chaperoning its folded RNA binding domain.
Elife, 10 Art. No. e69377 (2021)
Open Access PubMed Source   

Aberrant liquid-to-solid phase transitions of biomolecular condensates have been linked to various neurodegenerative diseases. However, the underlying molecular interactions that drive aging remain enigmatic. Here, we develop quantitative time-resolved crosslinking mass spectrometry to monitor protein interactions and dynamics inside condensates formed by the protein fused in sarcoma (FUS). We identify misfolding of the RNA recognition motif (RRM) of FUS as a key driver of condensate ageing. We demonstrate that the small heat shock protein HspB8 partitions into FUS condensates via its intrinsically disordered domain and prevents condensate hardening via condensate-specific interactions that are mediated by its α-crystallin domain (αCD). These αCD-mediated interactions are altered in a disease-associated mutant of HspB8, which abrogates the ability of HspB8 to prevent condensate hardening. We propose that stabilizing aggregation-prone folded RNA-binding domains inside condensates by molecular chaperones may be a general mechanism to prevent aberrant phase transitions.
@article{Boczek8179,
author={Edgar Boczek, Julius Fürsch, Marie Laura Niedermeier, Louise Jawerth, Marcus Jahnel, Martine Ruer-Gruß, Kai-Michael Kammer, Paul J Heid, Laura Mediani, Jie Wang, Xiao Yan, Andrei Pozniakovski, Ina Poser, Daniel Mateju, Lars Hubatsch, Serena Carra, Dr Simon Alberti, Anthony Hyman, Florian Stengel},
title={HspB8 prevents aberrant phase transitions of FUS by chaperoning its folded RNA binding domain.},
journal ={eLife},
volume={10},
pages={null--null},
year=2021
}


✳︎ joined first author, # joined corresponding author