@article{18934,
  abstract     = {The assembly of biomolecular condensate in eukaryotic cells and the accumulation of amyloid deposits in neurons are processes involving the nucleation and growth (NAG) of new protein phases. To therapeutically target protein phase separation, drug candidates are tested in in vitro assays that monitor the increase in the mass or size of the new phase. Limited mechanistic insight is, however, provided if empirical or untestable kinetic models are fitted to these progress curves. Here we present the web server NAGPKin that quantifies NAG rates using mass-based or size-based progress curves as the input data. A report is generated containing the fitted NAG parameters and elucidating the phase separation mechanisms at play. The NAG parameters can be used to predict particle size distributions of, for example, protein droplets formed by liquid-liquid phase separation (LLPS) or amyloid fibrils formed by protein aggregation. Because minimal intervention is required from the user, NAGPKin is a good platform for standardized reporting of LLPS and protein self-assembly data. NAGPKin is useful for drug discovery as well as for fundamental studies on protein phase separation. NAGPKin is freely available (no login required) at https://nagpkin.i3s.up.pt .},
  author       = {Sárkány, Zsuzsa and Figueiredo, Francisco and Macedo-Ribeiro, Sandra and Martins, Pedro M.},
  issn         = {1939-4586},
  journal      = {Molecular Biology of the Cell},
  number       = {3},
  publisher    = {American Society for Cell Biology},
  title        = {{NAGPKin: Nucleation-and-growth parameters from the kinetics of protein phase separation}},
  doi          = {10.1091/mbc.e23-07-0289},
  volume       = {35},
  year         = {2024},
}

@article{9414,
  abstract     = {Microtubule plus-end depolymerization rate is a potentially important target of physiological regulation, but it has been challenging to measure, so its role in spatial organization is poorly understood. Here we apply a method for tracking plus ends based on time difference imaging to measure depolymerization rates in large interphase asters growing in Xenopus egg extract. We observed strong spatial regulation of depolymerization rates, which were higher in the aster interior compared with the periphery, and much less regulation of polymerization or catastrophe rates. We interpret these data in terms of a limiting component model, where aster growth results in lower levels of soluble tubulin and microtubule-associated proteins (MAPs) in the interior cytosol compared with that at the periphery. The steady-state polymer fraction of tubulin was ∼30%, so tubulin is not strongly depleted in the aster interior. We propose that the limiting component for microtubule assembly is a MAP that inhibits depolymerization, and that egg asters are tuned to low microtubule density.},
  author       = {Ishihara, Keisuke and Decker, Franziska and Dos Santos Caldas, Paulo R and Pelletier, James F. and Loose, Martin and Brugués, Jan and Mitchison, Timothy J.},
  issn         = {1939-4586},
  journal      = {Molecular Biology of the Cell},
  number       = {9},
  pages        = {869--879},
  publisher    = {American Society for Cell Biology},
  title        = {{Spatial variation of microtubule depolymerization in large asters}},
  doi          = {10.1091/MBC.E20-11-0723},
  volume       = {32},
  year         = {2021},
}

@article{698,
  abstract     = {Extracellular matrix signals from the microenvironment regulate gene expression patterns and cell behavior. Using a combination of experiments and geometric models, we demonstrate correlations between cell geometry, three-dimensional (3D) organization of chromosome territories, and gene expression. Fluorescence in situ hybridization experiments showed that micropatterned fibroblasts cultured on anisotropic versus isotropic substrates resulted in repositioning of specific chromosomes, which contained genes that were differentially regulated by cell geometries. Experiments combined with ellipsoid packing models revealed that the mechanosensitivity of chromosomes was correlated with their orientation in the nucleus. Transcription inhibition experiments suggested that the intermingling degree was more sensitive to global changes in transcription than to chromosome radial positioning and its orientations. These results suggested that cell geometry modulated 3D chromosome arrangement, and their neighborhoods correlated with gene expression patterns in a predictable manner. This is central to understanding geometric control of genetic programs involved in cellular homeostasis and the associated diseases. },
  author       = {Wang, Yejun and Nagarajan, Mallika and Uhler, Caroline and Shivashankar, Gv},
  issn         = {1059-1524},
  journal      = {Molecular Biology of the Cell},
  number       = {14},
  pages        = {1997 -- 2009},
  publisher    = {American Society for Cell Biology},
  title        = {{Orientation and repositioning of chromosomes correlate with cell geometry dependent gene expression}},
  doi          = {10.1091/mbc.E16-12-0825},
  volume       = {28},
  year         = {2017},
}

@article{11082,
  abstract     = {The nuclear pore complex (NPC) plays a critical role in gene expression by mediating import of transcription regulators into the nucleus and export of RNA transcripts to the cytoplasm. Emerging evidence suggests that in addition to mediating transport, a subset of nucleoporins (Nups) engage in transcriptional activation and elongation at genomic loci that are not associated with NPCs. The underlying mechanism and regulation of Nup mobility on and off nuclear pores remain unclear. Here we show that Nup50 is a mobile Nup with a pronounced presence both at the NPC and in the nucleoplasm that can move between these different localizations. Strikingly, the dynamic behavior of Nup50 in both locations is dependent on active transcription by RNA polymerase II and requires the N-terminal half of the protein, which contains importin α– and Nup153-binding domains. However, Nup50 dynamics are independent of importin α, Nup153, and Nup98, even though the latter two proteins also exhibit transcription-dependent mobility. Of interest, depletion of Nup50 from C2C12 myoblasts does not affect cell proliferation but inhibits differentiation into myotubes. Taken together, our results suggest a transport-independent role for Nup50 in chromatin biology that occurs away from the NPC.},
  author       = {Buchwalter, Abigail L. and Liang, Yun and HETZER, Martin W},
  issn         = {1059-1524},
  journal      = {Molecular Biology of the Cell},
  keywords     = {Cell Biology, Molecular Biology},
  number       = {16},
  pages        = {2472--2484},
  publisher    = {American Society for Cell Biology},
  title        = {{Nup50 is required for cell differentiation and exhibits transcription-dependent dynamics}},
  doi          = {10.1091/mbc.e14-04-0865},
  volume       = {25},
  year         = {2014},
}

