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Theerthagiri G.,Friedrich Miescher Laboratory of the Max Planck Society | Eisenhardt N.,Friedrich Miescher Laboratory of the Max Planck Society | Schwarz H.,Max Planck Institute for Developmental Biology | Antonin W.,Friedrich Miescher Laboratory of the Max Planck Society
Journal of Cell Biology | Year: 2010

All transport across the nuclear envelope (NE) is mediated by nuclear pore complexes (NPCs). Despite their enormous size, ∼60 MD in vertebrates, they are comprised of only ∼30 distinct proteins (nucleoporins or Nups), many of which form subcomplexes that act as building blocks for NPC assembly. One of these evolutionarily conserved subcomplexes, the Nup93 complex, is a major structural component linking the NPC to the membranes of the NE. Using in vitro nuclear assembly assays, we show that two components of the Nup93 complex, Nup188 and Nup205, are dispensable for NPC formation. However, nuclei lacking Nup188 increase in size by several fold compared with wild type. We demonstrate that this phenotype is caused by an accelerated translocation of integral membrane proteins through NPCs, suggesting that Nup188 confines the passage of membrane proteins and is thus crucial for the homeostasis of the different nuclear membranes. © 2010 Theerthagiri et al.


Sakuno T.,University of Tokyo | Tanaka K.,University of Tokyo | Hauf S.,Friedrich Miescher Laboratory of the Max Planck Society | Watanabe Y.,University of Tokyo
Developmental Cell | Year: 2011

During meiosis I, kinetochores of sister chromatids are juxtaposed or fused and mono-orient, while homologous chromosomes that are paired by chiasmata (bivalents) have to biorient. In the absence of chiasmata, biorientation of sister chromatids (univalents), which carries a risk of aneuploidy, has been occasionally detected in several species, including humans. We show in fission yeast that biorientation of fused sister kinetochores predominates during early prometaphase I. Without chiasmata, this undesirable biorientation of univalents persists and eventually evades the spindle assembly checkpoint, provoking abnormal anaphase. When univalents are connected by chiasmata or by an artificial tether, this erroneous attachment is converted to monopolar attachment and stabilized. This stabilization is apparently achieved by a chromosome configuration that brings kinetochores to the outer edge of the bivalent, while bringing Aurora B, a destabilizer of kinetochore-microtubule attachment, inward. Our results elucidate how chiasmata favor biorientation of bivalents over that of univalents at meiosis I. © 2011 Elsevier Inc.


Antonin W.,Friedrich Miescher Laboratory of the Max Planck Society
Nucleus (Austin, Tex.) | Year: 2011

The inner nuclear membrane (INM) accommodates a specific set of integral membrane proteins many of which interact with chromatin and/or in metazoan cells with the lamina network. The localization of these proteins characterizes this membrane area of the nuclear envelope (NE) despite the fact that the INM forms a membrane continuum with the outer nuclear membrane (ONM) and the remaining endoplasmic reticulum (ER). In fact, the INM can be regarded as a highly specialized membrane subdomain of the ER. How the specific protein composition of the INM is established and maintained and whether this is achieved via a single unifying mechanism is by and large unclear. Recent experiments shed light on some aspects of the process.


Eisenhardt N.,Friedrich Miescher Laboratory of the Max Planck Society | Redolfi J.,Friedrich Miescher Laboratory of the Max Planck Society | Antonin W.,Friedrich Miescher Laboratory of the Max Planck Society
Journal of Cell Science | Year: 2014

Nuclear pore complexes (NPCs) are the gateways for nucleocytoplasmic exchange. The ordered assembly of these huge complexes from several hundred individual components into an intricate protein interaction network which deforms the two membranes of the nuclear envelope into a pore is only rudimentarily understood. Here, we show that the interaction between Nup53 and the integral pore membrane protein Ndc1 is essential for vertebrate NPC assembly. The Ndc1 binding site on Nup53 overlaps with a region that induces membrane bending and is specifically required to modulate this activity, suggesting that the membrane-deforming capability of Nup53 is adjusted during the NPC assembly process. We further demonstrate that the interaction of Nup53 and Nup155 has a crucial role in NPC formation as the main determinant of recruitment of Nup155 to the assembling pore. Overall, our results pinpoint the diversity of interaction modes accomplished by Nup53, highlighting this protein as an essential link between the pore membrane and the NPC, and as a crucial factor in the formation of the pore membrane. © 2014. Published by The Company of Biologists Ltd.


Hauf S.,Friedrich Miescher Laboratory of the Max Planck Society
Biochemical Society Transactions | Year: 2013

The spindle assembly checkpoint is a conserved mitotic signalling pathway that ensures the equal segregation of chromosomes to daughter cells. Despite intensive work in many model organisms, key features of this safety mechanism remain unexplained. In the present review, I briefly summarize advances made in the last few years, and then focus on unexplored corners of this signalling pathway. © 2013 Biochemical Society.


Lochmann B.,Friedrich Miescher Laboratory of the Max Planck Society | Ivanov D.,Friedrich Miescher Laboratory of the Max Planck Society
PLoS Genetics | Year: 2012

During cell division, segregation of sister chromatids to daughter cells is achieved by the poleward pulling force of microtubules, which attach to the chromatids by means of a multiprotein complex, the kinetochore. Kinetochores assemble at the centromeric DNA organized by specialized centromeric nucleosomes. In contrast to other eukaryotes, which typically have large repetitive centromeric regions, budding yeast CEN DNA is defined by a 125 bp sequence and assembles a single centromeric nucleosome. In budding yeast, as well as in other eukaryotes, the Cse4 histone variant (known in vertebrates as CENP-A) is believed to substitute for histone H3 at the centromeric nucleosome. However, the exact composition of the CEN nucleosome remains a subject of debate. We report the use of a novel ChIP approach to reveal the composition of the centromeric nucleosome and its localization on CEN DNA in budding yeast. Surprisingly, we observed a strong interaction of H3, as well as Cse4, H4, H2A, and H2B, but not histone chaperone Scm3 (HJURP in human) with the centromeric DNA. H3 localizes to centromeric DNA at all stages of the cell cycle. Using a sequential ChIP approach, we could demonstrate the co-occupancy of H3 and Cse4 at the CEN DNA. Our results favor a H3-Cse4 heterotypic octamer at the budding yeast centromere. Whether or not our model is correct, any future model will have to account for the stable association of histone H3 with the centromeric DNA. © 2012 Lochmann, Ivanov.


Vollmer B.,Friedrich Miescher Laboratory of the Max Planck Society | Antonin W.,Friedrich Miescher Laboratory of the Max Planck Society
Biological Chemistry | Year: 2014

Nuclear pore complexes mediate the transport between the cell nucleoplasm and cytoplasm. These 125 MDa structures are among the largest assemblies found in eukaryotes, built from proteins organized in distinct subcomplexes that act as building blocks during nuclear pore complex biogenesis. In this review, we focus on one of these subcomplexes, the Nup93 complex in metazoa and its yeast counterpart, the Nic96 complex. We discuss its essential function in nuclear pore complex assembly as a linker between the nuclear membrane and the central part of the pore and its various roles in nuclear transport processes and beyond.


Bohnert R.,Friedrich Miescher Laboratory of the Max Planck Society | Ratsch G.,Friedrich Miescher Laboratory of the Max Planck Society
Nucleic Acids Research | Year: 2010

We provide a novel web service, called rQuant.web, allowing convenient access to tools for quantitative analysis of RNA sequencing data. The underlying quantitation technique rQuant is based on quadratic programming and estimates different biases induced by library preparation, sequencing and read mapping. It can tackle multiple transcripts per gene locus and is therefore particularly well suited to quantify alternative transcripts. rQuant.web is available as a tool in a Galaxy installation at http://galaxy.fml.mpg.de. Using rQuant.web is free of charge, it is open to all users, and there is no login requirement. © The Author(s) 2010. Published by Oxford University Press.


Antonin W.,Friedrich Miescher Laboratory of the Max Planck Society
EMBO Journal | Year: 2013

Eukaryotic cells critically rely on a constant and intensive exchange of macromolecules between the cytoplasm and nucleoplasm across the barrier of the nuclear envelope. Nuclear pore complexes (NPCs) function as gates to mediate this transport, but why they grant the selective passage of transport receptor-cargo complexes and at the same time exclude most other cellular macromolecules is incompletely understood. In this issue of The EMBO Journal, Labokha et al (2013) extend our view on how certain NPC proteins form a sieve-like meshwork within the pore that is crucial for these functions. © 2013 European Molecular Biology Organization.


News Article | April 26, 2016
Site: phys.org

When new life develops, a tiny ball of initially identical cells has to form the different body parts of the mature organism. Sixty years ago, Alan Turing proposed that this body patterning is achieved by two types of signaling molecules that spread in the developing tissues to create a spatial pattern. Scientists from the Friedrich Miescher Laboratory of the Max Planck Society in Tübingen have now developed new mathematical approaches and software to systematically analyze realistic pattern forming networks that involve more than two molecules. The software can be used to analyze how patterns form during development and to create novel patterns for bioengineering approaches.

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