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Oliver Beutel, Riccardo Maraspini, Karina Pombo-García, Cécilie Martin-Lemaitre, Alf Honigmann
Phase Separation of Zonula Occludens Proteins Drives Formation of Tight Junctions.
Cell, 179(4) 923-936 (2019)
PubMed Source   

Tight junctions are cell-adhesion complexes that seal tissues and are involved in cell polarity and signaling. Supra-molecular assembly and positioning of tight junctions as continuous networks of adhesion strands are dependent on the membrane-associated scaffolding proteins ZO1 and ZO2. To understand how zona occludens (ZO) proteins organize junction assembly, we performed quantitative cell biology and in vitro reconstitution experiments. We discovered that ZO proteins self-organize membrane-attached compartments via phase separation. We identified the multivalent interactions of the conserved PDZ-SH3-GuK supra-domain as the driver of phase separation. These interactions are regulated by phosphorylation and intra-molecular binding. Formation of condensed ZO protein compartments is sufficient to specifically enrich and localize tight-junction proteins, including adhesion receptors, cytoskeletal adapters, and transcription factors. Our results suggest that an active-phase transition of ZO proteins into a condensed membrane-bound compartment drives claudin polymerization and coalescence of a continuous tight-junction belt.
@article{Beutel7537,
author={Oliver Beutel, Riccardo Maraspini, Karina Pombo-García, Cécilie Martin-Lemaitre, Alf Honigmann},
title={Phase Separation of Zonula Occludens Proteins Drives Formation of Tight Junctions.},
journal ={Cell},
volume={179},
issue ={4},
pages={923--936},
year=2019
}

Bogdan Kirilenko, Lee R Hagey, Stephen Barnes, Charles N Falany, Michael Hiller
Evolutionary analysis of bile acid-conjugating enzymes reveals a complex duplication and reciprocal loss history.
Genome Biol Evol, Art. No. doi: 10.1093/gbe/evz238 (2019)
PubMed Source   

To fulfill their physiological functions, bile acids are conjugated with amino acids. In humans, conjugation is catalyzed by bile acid coenzyme A:amino acid N-acyltransferase (BAAT), an enzyme with a highly-conserved catalytic triad in its active site. Interestingly, the conjugated amino acids are highly variable among mammals, with some species conjugating bile acids with both glycine and taurine, whereas others conjugate only taurine. The genetic origin of these bile acid conjugation differences is unknown. Here, we tested whether mutations in BAAT's catalytic triad could explain bile acid conjugation differences. Our comparative analysis of 118 mammals first revealed that the ancestor of placental mammals and marsupials possessed two genes, BAAT and BAATP1, that arose by a tandem duplication. This duplication was followed by numerous gene losses, including BAATP1 in humans. Losses of either BAAT or BAATP1 largely happened in a reciprocal fashion, suggesting that a single conjugating enzyme is generally sufficient for mammals. In intact BAAT and BAATP1 genes, we observed multiple changes in the catalytic triad between Cys and Ser residues. Surprisingly, while mutagenesis experiments with the human enzyme have shown that replacing Cys for Ser greatly diminishes the glycine-conjugating ability, across mammals we found that this residue provides little power in predicting the experimentally-measured amino acids that are conjugated with bile acids. This suggests that the mechanism of BAAT's enzymatic function is incompletely understood, despite relying on a classic catalytic triad. More generally, our evolutionary analysis indicates that results of mutagenesis experiments may not easily be extrapolatable to other species.
@article{Kirilenko7538,
author={Bogdan Kirilenko, Lee R Hagey, Stephen Barnes, Charles N Falany, Michael Hiller},
title={Evolutionary analysis of bile acid-conjugating enzymes reveals a complex duplication and reciprocal loss history.},
journal ={Genome biology and evolution},
volume={},
pages={1--1},
year=2019
}

Pavel Vopalensky, Maria Antonietta Tosches, Kaia Achim, Mette Handberg-Thorsager, Detlev Arendt
From spiral cleavage to bilateral symmetry: the developmental cell lineage of the annelid brain.
BMC Biol, 17(1) Art. No. 81 (2019)
PubMed Source   

During early development, patterns of cell division-embryonic cleavage-accompany the gradual restriction of blastomeres to specific cell fates. In Spiralia, which include annelids, mollusks, and flatworms, "spiral cleavage" produces a highly stereotypic, spiral-like arrangement of blastomeres and swimming trochophore-type larvae with rotational (spiral) symmetry. However, starting at larval stages, spiralian larvae acquire elements of bilateral symmetry, before they metamorphose into fully bilateral juveniles. How this spiral-to-bilateral transition occurs is not known and is especially puzzling for the early differentiating brain and head sensory organs, which emerge directly from the spiral cleavage pattern. Here we present the developmental cell lineage of the Platynereis larval episphere.
@article{Vopalensky7530,
author={Pavel Vopalensky, Maria Antonietta Tosches, Kaia Achim, Mette Handberg-Thorsager, Detlev Arendt},
title={From spiral cleavage to bilateral symmetry: the developmental cell lineage of the annelid brain.},
journal ={BMC biology},
volume={17},
issue ={1},
pages={null--null},
year=2019
}

Johannes Baumgart, Marcel Kirchner, Stefanie Redemann, Alec Bond, Jeffrey Woodruff, Jean-Marc Verbavatz, Frank Jülicher, Thomas Müller-Reichert, Anthony Hyman, Jan Brugués
Soluble tubulin is significantly enriched at mitotic centrosomes.
J Cell Biol, Art. No. doi: 10.1083/jcb.201902069 (2019)
PubMed Source   

During mitosis, the centrosome expands its capacity to nucleate microtubules. Understanding the mechanisms of centrosomal microtubule nucleation is, however, constrained by a lack of knowledge of the amount of soluble and polymeric tubulin at mitotic centrosomes. Here we combined light microscopy and serial-section electron tomography to measure the amount of dimeric and polymeric tubulin at mitotic centrosomes in early C. elegans embryos. We show that a C. elegans one-cell stage centrosome at metaphase contains >10,000 microtubules with a total polymer concentration of 230 µM. Centrosomes concentrate soluble α/β tubulin by about 10-fold over the cytoplasm, reaching peak values of 470 µM, giving a combined total monomer and polymer tubulin concentration at centrosomes of up to 660 µM. These findings support in vitro data suggesting that microtubule nucleation in C. elegans centrosomes is driven in part by concentrating soluble tubulin.
@article{Baumgart7536,
author={Johannes Baumgart, Marcel Kirchner, Stefanie Redemann, Alec Bond, Jeffrey Woodruff, Jean-Marc Verbavatz, Frank Jülicher, Thomas Müller-Reichert, Anthony Hyman, Jan Brugués},
title={Soluble tubulin is significantly enriched at mitotic centrosomes.},
journal ={The Journal of cell biology},
volume={},
pages={1--1},
year=2019
}

Moritz Kreysing
Probing the Functional Role of Physical Motion in Development.
Dev Cell, 51(2) 135-144 (2019)
PubMed Source   

Spatiotemporal organization during development has frequently been proposed to be explainable by reaction-transport models, where biochemical reactions couple to physical motion. However, whereas genetic tools allow causality of molecular players to be dissected via perturbation experiments, the functional role of physical transport processes, such as diffusion and cytoplasmic streaming, frequently remains untestable. This Perspective explores the challenges of validating reaction-transport hypotheses and highlights new opportunities provided by perturbation approaches that specifically target physical transport mechanisms. Using these methods, experimental physics may begin to catch up with molecular biology and find ways to test roles of diffusion and flows in development.
@article{Kreysing7528,
author={Moritz Kreysing},
title={Probing the Functional Role of Physical Motion in Development.},
journal ={Developmental cell},
volume={51},
issue ={2},
pages={135--144},
year=2019
}

Pavel Tomancak
Evolutionary history of tissue bending.
Science, 366(6463) 300-301 (2019)
PubMed Source  

@article{Tomancak7531,
author={Pavel Tomancak},
title={Evolutionary history of tissue bending.},
journal ={Science (New York, N.Y.)},
volume={366},
issue ={6463},
pages={300--301},
year=2019
}

Patryk Burek, Nico Scherf, Heinrich Herre
Ontology patterns for the representation of quality changes of cells in time.
J Biomed Semantics, 10(1) Art. No. 16 (2019)
PubMed Source   

Cell tracking experiments, based on time-lapse microscopy, have become an important tool in biomedical research. The goal is the reconstruction of cell migration patterns, shape and state changes, and, comprehensive genealogical information from these data. This information can be used to develop process models of cellular dynamics. However, so far there has been no structured, standardized way of annotating and storing the tracking results, which is critical for comparative analysis and data integration. The key requirement to be satisfied by an ontology is the representation of a cell's change over time. Unfortunately, popular ontology languages, such as Web Ontology Language (OWL), have limitations for the representation of temporal information. The current paper addresses the fundamental problem of modeling changes of qualities over time in biomedical ontologies specified in OWL.
@article{Burek7534,
author={Patryk Burek, Nico Scherf, Heinrich Herre},
title={Ontology patterns for the representation of quality changes of cells in time.},
journal ={Journal of biomedical semantics},
volume={10},
issue ={1},
pages={null--null},
year=2019
}

Hauke Drechsler, Yong Xu, Veikko Geyer, Yixin Zhang, Stefan Diez
Multivalent electrostatic microtubule-interactions of synthetic peptides are sufficient to mimic advanced MAP-like behaviour.
Mol Biol Cell, Art. No. doi: 10.1091/mbc.E19-05-0247 (2019)
PubMed Source   

Microtubule associated proteins (MAPs) are a functionally highly diverse class of proteins that help to adjust the shape and function of the microtubule cytoskeleton in space and time. For this purpose, MAPs structurally support microtubules, modulate their dynamic instability or regulate the activity of associated molecular motors. The microtubule binding domains of MAPs are structurally divergent, but often depend on electrostatic interactions with the negatively charged surface of the microtubule. This suggests that the surface exposure of positive charges rather than a certain structural fold is sufficient for a protein to associate with microtubules. Consistently, positively charged artificial objects have been shown to associate with microtubules and to diffuse along their lattice. Natural MAPs, however, show a more sophisticated functionality beyond lattice-diffusion. Here we asked, whether basic electrostatic interactions are sufficient to also support advanced MAP-functionality. To test this hypothesis, we studied simple positively charged peptide sequences for the occurrence of typical MAP-like behaviour. We found that a multivalent peptide construct featuring four lysine-alanine heptarepeats (starPEG-(KA7)4) - but not its monovalent KA7-subunits - show advanced, biologically relevant MAP-like behaviour: starPEG-(KA7)4 binds microtubules in the low nanomolar range, diffuses along their lattice with the ability to switch between intersecting microtubules and tracks depolymerising microtubule ends. Further, starPEG-(KA7)4 promotes microtubule nucleation and growth, mediates depolymerisation coupled pulling at plus ends and bundles microtubules without significantly interfering with other proteins on the microtubule lattice (as exemplified by the motor kinesin-1). Our results show that positive charges and multivalency are sufficient to mimic advanced MAP-like behaviour. [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text] [Media: see text].
@article{Drechsler7535,
author={Hauke Drechsler, Yong Xu, Veikko Geyer, Yixin Zhang, Stefan Diez},
title={Multivalent electrostatic microtubule-interactions of synthetic peptides are sufficient to mimic advanced MAP-like behaviour.},
journal ={Molecular biology of the cell},
volume={},
pages={19050247--19050247},
year=2019
}

Mohammad A Rahman, Cordula Reuther, Frida W Lindberg, Martina Mengoni, Aseem Salhotra, Georg Heldt, Heiner Linke, Stefan Diez, Alf Månsson
Regeneration of Assembled, Molecular-Motor-Based Bionanodevices.
Nano Lett, 19(10) 7155-7163 (2019)
PubMed Source   

The guided gliding of cytoskeletal filaments, driven by biomolecular motors on nano/microstructured chips, enables novel applications in biosensing and biocomputation. However, expensive and time-consuming chip production hampers the developments. It is therefore important to establish protocols to regenerate the chips, preferably without the need to dismantle the assembled microfluidic devices which contain the structured chips. We here describe a novel method toward this end. Specifically, we use the small, nonselective proteolytic enzyme, proteinase K to cleave all surface-adsorbed proteins, including myosin and kinesin motors. Subsequently, we apply a detergent (5% SDS or 0.05% Triton X100) to remove the protein remnants. After this procedure, fresh motor proteins and filaments can be added for new experiments. Both, silanized glass surfaces for actin-myosin motility and pure glass surfaces for microtubule-kinesin motility were repeatedly regenerated using this approach. Moreover, we demonstrate the applicability of the method for the regeneration of nano/microstructured silicon-based chips with selectively functionalized areas for supporting or suppressing gliding motility for both motor systems. The results substantiate the versatility and a promising broad use of the method for regenerating a wide range of protein-based nano/microdevices.
@article{Rahman7517,
author={Mohammad A Rahman, Cordula Reuther, Frida W Lindberg, Martina Mengoni, Aseem Salhotra, Georg Heldt, Heiner Linke, Stefan Diez, Alf Månsson},
title={Regeneration of Assembled, Molecular-Motor-Based Bionanodevices.},
journal ={Nano letters},
volume={19},
issue ={10},
pages={7155--7163},
year=2019
}

Iskra Yanakieva, Anna Erzberger, Marija Matejčić, Carl D. Modes, Caren Norden
Cell and tissue morphology determine actin-dependent nuclear migration mechanisms in neuroepithelia.
J Cell Biol, 218(10) 3272-3289 (2019)
PubMed Source   

Correct nuclear position is crucial for cellular function and tissue development. Depending on cell context, however, the cytoskeletal elements responsible for nuclear positioning vary. While these cytoskeletal mechanisms have been intensely studied in single cells, how nuclear positioning is linked to tissue morphology is less clear. Here, we compare apical nuclear positioning in zebrafish neuroepithelia. We find that kinetics and actin-dependent mechanisms of nuclear positioning vary in tissues of different morphology. In straight neuroepithelia, nuclear positioning is controlled by Rho-ROCK-dependent myosin contractility. In contrast, in basally constricted neuroepithelia, a novel formin-dependent pushing mechanism is found for which we propose a proof-of-principle force generation theory. Overall, our data suggest that correct nuclear positioning is ensured by the adaptability of the cytoskeleton to cell and tissue shape. This in turn leads to robust epithelial maturation across geometries. The conclusion that different nuclear positioning mechanisms are favored in tissues of different morphology highlights the importance of developmental context for the execution of intracellular processes.
@article{Yanakieva7484,
author={Iskra Yanakieva, Anna Erzberger, Marija Matejčić, Carl D. Modes, Caren Norden},
title={Cell and tissue morphology determine actin-dependent nuclear migration mechanisms in neuroepithelia.},
journal ={The Journal of cell biology},
volume={218},
issue ={10},
pages={3272--3289},
year=2019
}