@article{14826, abstract = {The plant-signaling molecule auxin triggers fast and slow cellular responses across land plants and algae. The nuclear auxin pathway mediates gene expression and controls growth and development in land plants, but this pathway is absent from algal sister groups. Several components of rapid responses have been identified in Arabidopsis, but it is unknown if these are part of a conserved mechanism. We recently identified a fast, proteome-wide phosphorylation response to auxin. Here, we show that this response occurs across 5 land plant and algal species and converges on a core group of shared targets. We found conserved rapid physiological responses to auxin in the same species and identified rapidly accelerated fibrosarcoma (RAF)-like protein kinases as central mediators of auxin-triggered phosphorylation across species. Genetic analysis connects this kinase to both auxin-triggered protein phosphorylation and rapid cellular response, thus identifying an ancient mechanism for fast auxin responses in the green lineage.}, author = {Kuhn, Andre and Roosjen, Mark and Mutte, Sumanth and Dubey, Shiv Mani and Carrillo Carrasco, Vanessa Polet and Boeren, Sjef and Monzer, Aline and Koehorst, Jasper and Kohchi, Takayuki and Nishihama, Ryuichi and Fendrych, Matyas and Sprakel, Joris and Friml, Jiří and Weijers, Dolf}, issn = {1097-4172}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {1}, pages = {130--148.e17}, publisher = {Elsevier}, title = {{RAF-like protein kinases mediate a deeply conserved, rapid auxin response}}, doi = {10.1016/j.cell.2023.11.021}, volume = {187}, year = {2024}, } @article{12802, abstract = {Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead to autism, we employed metabolomic profiling to study the metabolic states of the cerebral cortex across different developmental stages. We found that the forebrain undergoes significant metabolic remodeling throughout development, with certain groups of metabolites showing stage-specific changes, but what are the consequences of perturbing this metabolic program? By manipulating Slc7a5 expression in neural cells, we found that the metabolism of LNAAs and lipids are interconnected in the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state, leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction.}, author = {Knaus, Lisa and Basilico, Bernadette and Malzl, Daniel and Gerykova Bujalkova, Maria and Smogavec, Mateja and Schwarz, Lena A. and Gorkiewicz, Sarah and Amberg, Nicole and Pauler, Florian and Knittl-Frank, Christian and Tassinari, Marianna and Maulide, Nuno and Rülicke, Thomas and Menche, Jörg and Hippenmeyer, Simon and Novarino, Gaia}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {9}, pages = {1950--1967.e25}, publisher = {Elsevier}, title = {{Large neutral amino acid levels tune perinatal neuronal excitability and survival}}, doi = {10.1016/j.cell.2023.02.037}, volume = {186}, year = {2023}, } @article{10573, abstract = {How tissues acquire complex shapes is a fundamental question in biology and regenerative medicine. Zebrafish semicircular canals form from invaginations in the otic epithelium (buds) that extend and fuse to form the hubs of each canal. We find that conventional actomyosin-driven behaviors are not required. Instead, local secretion of hyaluronan, made by the enzymes uridine 5′-diphosphate dehydrogenase (ugdh) and hyaluronan synthase 3 (has3), drives canal morphogenesis. Charged hyaluronate polymers osmotically swell with water and generate isotropic extracellular pressure to deform the overlying epithelium into buds. The mechanical anisotropy needed to shape buds into tubes is conferred by a polarized distribution of actomyosin and E-cadherin-rich membrane tethers, which we term cytocinches. Most work on tissue morphogenesis ascribes actomyosin contractility as the driving force, while the extracellular matrix shapes tissues through differential stiffness. Our work inverts this expectation. Hyaluronate pressure shaped by anisotropic tissue stiffness may be a widespread mechanism for powering morphological change in organogenesis and tissue engineering.}, author = {Munjal, Akankshi and Hannezo, Edouard B and Tsai, Tony Y.C. and Mitchison, Timothy J. and Megason, Sean G.}, issn = {1097-4172}, journal = {Cell}, number = {26}, pages = {6313--6325.e18}, publisher = {Elsevier ; Cell Press}, title = {{Extracellular hyaluronate pressure shaped by cellular tethers drives tissue morphogenesis}}, doi = {10.1016/j.cell.2021.11.025}, volume = {184}, year = {2021}, } @article{10348, abstract = {The endosomal sorting complex required for transport-III (ESCRT-III) catalyzes membrane fission from within membrane necks, a process that is essential for many cellular functions, from cell division to lysosome degradation and autophagy. How it breaks membranes, though, remains unknown. Here, we characterize a sequential polymerization of ESCRT-III subunits that, driven by a recruitment cascade and by continuous subunit-turnover powered by the ATPase Vps4, induces membrane deformation and fission. During this process, the exchange of Vps24 for Did2 induces a tilt in the polymer-membrane interface, which triggers transition from flat spiral polymers to helical filament to drive the formation of membrane protrusions, and ends with the formation of a highly constricted Did2-Ist1 co-polymer that we show is competent to promote fission when bound on the inside of membrane necks. Overall, our results suggest a mechanism of stepwise changes in ESCRT-III filament structure and mechanical properties via exchange of the filament subunits to catalyze ESCRT-III activity.}, author = {Pfitzner, Anna-Katharina and Mercier, Vincent and Jiang, Xiuyun and Moser von Filseck, Joachim and Baum, Buzz and Šarić, Anđela and Roux, Aurélien}, issn = {0092-8674}, journal = {Cell}, keywords = {general biochemistry, genetics and molecular biology}, number = {5}, pages = {1140--1155.e18}, publisher = {Elsevier}, title = {{An ESCRT-III polymerization sequence drives membrane deformation and fission}}, doi = {10.1016/j.cell.2020.07.021}, volume = {182}, year = {2020}, } @article{6877, author = {Kopf, Aglaja and Sixt, Michael K}, issn = {1097-4172}, journal = {Cell}, number = {1}, pages = {51--53}, publisher = {Elsevier}, title = {{The neural crest pitches in to remove apoptotic debris}}, doi = {10.1016/j.cell.2019.08.047}, volume = {179}, year = {2019}, } @article{7001, author = {Schwayer, Cornelia and Shamipour, Shayan and Pranjic-Ferscha, Kornelija and Schauer, Alexandra and Balda, M and Tada, M and Matter, K and Heisenberg, Carl-Philipp J}, issn = {1097-4172}, journal = {Cell}, number = {4}, pages = {937--952.e18}, publisher = {Cell Press}, title = {{Mechanosensation of tight junctions depends on ZO-1 phase separation and flow}}, doi = {10.1016/j.cell.2019.10.006}, volume = {179}, year = {2019}, } @article{8436, abstract = {The exchange of metabolites between the mitochondrial matrix and the cytosol depends on β-barrel channels in the outer membrane and α-helical carrier proteins in the inner membrane. The essential translocase of the inner membrane (TIM) chaperones escort these proteins through the intermembrane space, but the structural and mechanistic details remain elusive. We have used an integrated structural biology approach to reveal the functional principle of TIM chaperones. Multiple clamp-like binding sites hold the mitochondrial membrane proteins in a translocation-competent elongated form, thus mimicking characteristics of co-translational membrane insertion. The bound preprotein undergoes conformational dynamics within the chaperone binding clefts, pointing to a multitude of dynamic local binding events. Mutations in these binding sites cause cell death or growth defects associated with impairment of carrier and β-barrel protein biogenesis. Our work reveals how a single mitochondrial “transfer-chaperone” system is able to guide α-helical and β-barrel membrane proteins in a “nascent chain-like” conformation through a ribosome-free compartment.}, author = {Weinhäupl, Katharina and Lindau, Caroline and Hessel, Audrey and Wang, Yong and Schütze, Conny and Jores, Tobias and Melchionda, Laura and Schönfisch, Birgit and Kalbacher, Hubert and Bersch, Beate and Rapaport, Doron and Brennich, Martha and Lindorff-Larsen, Kresten and Wiedemann, Nils and Schanda, Paul}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {5}, pages = {1365--1379.e25}, publisher = {Elsevier}, title = {{Structural basis of membrane protein chaperoning through the mitochondrial intermembrane space}}, doi = {10.1016/j.cell.2018.10.039}, volume = {175}, year = {2018}, } @article{11073, abstract = {Human cancer cells bear complex chromosome rearrangements that can be potential drivers of cancer development. However, the molecular mechanisms underlying these rearrangements have been unclear. Zhang et al. use a new technique combining live-cell imaging and single-cell sequencing to demonstrate that chromosomes mis-segregated to micronuclei frequently undergo chromothripsis-like rearrangements in the subsequent cell cycle.}, author = {Hatch, Emily M. and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {7}, pages = {1502--1504}, publisher = {Elsevier}, title = {{Linking micronuclei to chromosome fragmentation}}, doi = {10.1016/j.cell.2015.06.005}, volume = {161}, year = {2015}, } @article{11080, abstract = {The spindle assembly checkpoint prevents separation of sister chromatids until each kinetochore is attached to the mitotic spindle. Rodriguez-Bravo et al. report that the nuclear pore complex scaffolds spindle assembly checkpoint signaling in interphase, providing a store of inhibitory signals that limits the speed of the subsequent mitosis.}, author = {Buchwalter, Abigail and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {5}, pages = {868--869}, publisher = {Elsevier}, title = {{Nuclear pores set the speed limit for mitosis}}, doi = {10.1016/j.cell.2014.02.004}, volume = {156}, year = {2014}, } @article{6122, author = {Linneweber, Gerit A. and Jacobson, Jake and Busch, Karl Emanuel and Hudry, Bruno and Christov, Christo P. and Dormann, Dirk and Yuan, Michaela and Otani, Tomoki and Knust, Elisabeth and de Bono, Mario and Miguel-Aliaga, Irene}, issn = {0092-8674}, journal = {Cell}, number = {1-2}, pages = {69--83}, publisher = {Elsevier}, title = {{Neuronal control of metabolism through nutrient-dependent modulation of tracheal branching}}, doi = {10.1016/j.cell.2013.12.008}, volume = {156}, year = {2014}, } @article{9458, abstract = {Dnmt1 epigenetically propagates symmetrical CG methylation in many eukaryotes. Their genomes are typically depleted of CG dinucleotides because of imperfect repair of deaminated methylcytosines. Here, we extensively survey diverse species lacking Dnmt1 and show that, surprisingly, symmetrical CG methylation is nonetheless frequently present and catalyzed by a different DNA methyltransferase family, Dnmt5. Numerous Dnmt5-containing organisms that diverged more than a billion years ago exhibit clustered methylation, specifically in nucleosome linkers. Clustered methylation occurs at unprecedented densities and directly disfavors nucleosomes, contributing to nucleosome positioning between clusters. Dense methylation is enabled by a regime of genomic sequence evolution that enriches CG dinucleotides and drives the highest CG frequencies known. Species with linker methylation have small, transcriptionally active nuclei that approach the physical limits of chromatin compaction. These features constitute a previously unappreciated genome architecture, in which dense methylation influences nucleosome positions, likely facilitating nuclear processes under extreme spatial constraints.}, author = {Huff, Jason T. and Zilberman, Daniel}, issn = {1097-4172}, journal = {Cell}, number = {6}, pages = {1286--1297}, publisher = {Elsevier}, title = {{Dnmt1-independent CG methylation contributes to nucleosome positioning in diverse eukaryotes}}, doi = {10.1016/j.cell.2014.01.029}, volume = {156}, year = {2014}, } @article{11085, abstract = {During mitotic exit, missegregated chromosomes can recruit their own nuclear envelope (NE) to form micronuclei (MN). MN have reduced functioning compared to primary nuclei in the same cell, although the two compartments appear to be structurally comparable. Here we show that over 60% of MN undergo an irreversible loss of compartmentalization during interphase due to NE collapse. This disruption of the MN, which is induced by defects in nuclear lamina assembly, drastically reduces nuclear functions and can trigger massive DNA damage. MN disruption is associated with chromatin compaction and invasion of endoplasmic reticulum (ER) tubules into the chromatin. We identified disrupted MN in both major subtypes of human non-small-cell lung cancer, suggesting that disrupted MN could be a useful objective biomarker for genomic instability in solid tumors. Our study shows that NE collapse is a key event underlying MN dysfunction and establishes a link between aberrant NE organization and aneuploidy.}, author = {Hatch, Emily M. and Fischer, Andrew H. and Deerinck, Thomas J. and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {1}, pages = {47--60}, publisher = {Elsevier}, title = {{Catastrophic nuclear envelope collapse in cancer cell micronuclei}}, doi = {10.1016/j.cell.2013.06.007}, volume = {154}, year = {2013}, } @article{11087, abstract = {Intracellular proteins with long lifespans have recently been linked to age-dependent defects, ranging from decreased fertility to the functional decline of neurons. Why long-lived proteins exist in metabolically active cellular environments and how they are maintained over time remains poorly understood. Here, we provide a system-wide identification of proteins with exceptional lifespans in the rat brain. These proteins are inefficiently replenished despite being translated robustly throughout adulthood. Using nucleoporins as a paradigm for long-term protein persistence, we found that nuclear pore complexes (NPCs) are maintained over a cell’s life through slow but finite exchange of even its most stable subcomplexes. This maintenance is limited, however, as some nucleoporin levels decrease during aging, providing a rationale for the previously observed age-dependent deterioration of NPC function. Our identification of a long-lived proteome reveals cellular components that are at increased risk for damage accumulation, linking long-term protein persistence to the cellular aging process.}, author = {Toyama, Brandon H. and Savas, Jeffrey N. and Park, Sung Kyu and Harris, Michael S. and Ingolia, Nicholas T. and Yates, John R. and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {5}, pages = {971--982}, publisher = {Elsevier}, title = {{Identification of long-lived proteins reveals exceptional stability of essential cellular structures}}, doi = {10.1016/j.cell.2013.07.037}, volume = {154}, year = {2013}, } @article{9459, abstract = {Nucleosome remodelers of the DDM1/Lsh family are required for DNA methylation of transposable elements, but the reason for this is unknown. How DDM1 interacts with other methylation pathways, such as small-RNA-directed DNA methylation (RdDM), which is thought to mediate plant asymmetric methylation through DRM enzymes, is also unclear. Here, we show that most asymmetric methylation is facilitated by DDM1 and mediated by the methyltransferase CMT2 separately from RdDM. We find that heterochromatic sequences preferentially require DDM1 for DNA methylation and that this preference depends on linker histone H1. RdDM is instead inhibited by heterochromatin and absolutely requires the nucleosome remodeler DRD1. Together, DDM1 and RdDM mediate nearly all transposon methylation and collaborate to repress transposition and regulate the methylation and expression of genes. Our results indicate that DDM1 provides DNA methyltransferases access to H1-containing heterochromatin to allow stable silencing of transposable elements in cooperation with the RdDM pathway.}, author = {Zemach, Assaf and Kim, M. Yvonne and Hsieh, Ping-Hung and Coleman-Derr, Devin and Eshed-Williams, Leor and Thao, Ka and Harmer, Stacey L. and Zilberman, Daniel}, issn = {1097-4172}, journal = {Cell}, number = {1}, pages = {193--205}, publisher = {Elsevier}, title = {{The Arabidopsis nucleosome remodeler DDM1 allows DNA methyltransferases to access H1-containing heterochromatin}}, doi = {10.1016/j.cell.2013.02.033}, volume = {153}, year = {2013}, } @article{11090, abstract = {Nuclear export of mRNAs is thought to occur exclusively through nuclear pore complexes. In this issue of Cell, Speese et al. identify an alternate pathway for mRNA export in muscle cells where ribonucleoprotein complexes involved in forming neuromuscular junctions transit the nuclear envelope by fusing with and budding through the nuclear membrane.}, author = {Hatch, Emily M. and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {4}, pages = {733--735}, publisher = {Elsevier}, title = {{RNP export by nuclear envelope budding}}, doi = {10.1016/j.cell.2012.04.018}, volume = {149}, year = {2012}, } @article{11101, abstract = {In metazoa, nuclear pore complexes (NPCs) assemble from disassembled precursors into a reforming nuclear envelope (NE) at the end of mitosis and into growing intact NEs during interphase. Here, we show via RNAi-mediated knockdown that ELYS, a nucleoporin critical for the recruitment of the essential Nup107/160 complex to chromatin, is required for NPC assembly at the end of mitosis but not during interphase. Conversely, the transmembrane nucleoporin POM121 is critical for the incorporation of the Nup107/160 complex into new assembly sites specifically during interphase. Strikingly, recruitment of the Nup107/160 complex to an intact NE involves a membrane curvature-sensing domain of its constituent Nup133, which is not required for postmitotic NPC formation. Our results suggest that in organisms with open mitosis, NPCs assemble via two distinct mechanisms to accommodate cell cycle-dependent differences in NE topology.}, author = {Doucet, Christine M. and Talamas, Jessica A. and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {6}, pages = {1030--1041}, publisher = {Elsevier}, title = {{Cell cycle-dependent differences in nuclear pore complex assembly in metazoa}}, doi = {10.1016/j.cell.2010.04.036}, volume = {141}, year = {2010}, } @article{11102, abstract = {Nuclear pore complexes have recently been shown to play roles in gene activation; however their potential involvement in metazoan transcription remains unclear. Here we show that the nucleoporins Sec13, Nup98, and Nup88, as well as a group of FG-repeat nucleoporins, bind to the Drosophila genome at functionally distinct loci that often do not represent nuclear envelope contact sites. Whereas Nup88 localizes to silent loci, Sec13, Nup98, and a subset of FG-repeat nucleoporins bind to developmentally regulated genes undergoing transcription induction. Strikingly, RNAi-mediated knockdown of intranuclear Sec13 and Nup98 specifically inhibits transcription of their target genes and prevents efficient reactivation of transcription after heat shock, suggesting an essential role of NPC components in regulating complex gene expression programs of multicellular organisms.}, author = {Capelson, Maya and Liang, Yun and Schulte, Roberta and Mair, William and Wagner, Ulrich and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {3}, pages = {372--383}, publisher = {Elsevier}, title = {{Chromatin-bound nuclear pore components regulate gene expression in higher eukaryotes}}, doi = {10.1016/j.cell.2009.12.054}, volume = {140}, year = {2010}, } @article{7703, abstract = {By combining gene expression profiling with image registration, Tomer et al. (2010) find that the mushroom body of the segmented worm Platynereis dumerilii shares many features with the mammalian cerebral cortex. The authors propose that the mushroom body and cortex evolved from the same structure in the common ancestor of vertebrates and invertebrates.}, author = {Sweeney, Lora Beatrice Jaeger and Luo, Liqun}, issn = {0092-8674}, journal = {Cell}, number = {5}, pages = {679--681}, publisher = {Elsevier}, title = {{‘Fore brain: A hint of the ancestral cortex}}, doi = {10.1016/j.cell.2010.08.024}, volume = {142}, year = {2010}, } @article{11108, abstract = {In dividing cells, nuclear pore complexes (NPCs) disassemble during mitosis and reassemble into the newly forming nuclei. However, the fate of nuclear pores in postmitotic cells is unknown. Here, we show that NPCs, unlike other nuclear structures, do not turn over in differentiated cells. While a subset of NPC components, like Nup153 and Nup50, are continuously exchanged, scaffold nucleoporins, like the Nup107/160 complex, are extremely long-lived and remain incorporated in the nuclear membrane during the entire cellular life span. Besides the lack of nucleoporin expression and NPC turnover, we discovered an age-related deterioration of NPCs, leading to an increase in nuclear permeability and the leaking of cytoplasmic proteins into the nucleus. Our finding that nuclear “leakiness” is dramatically accelerated during aging and that a subset of nucleoporins is oxidatively damaged in old cells suggests that the accumulation of damage at the NPC might be a crucial aging event.}, author = {D'Angelo, Maximiliano A. and Raices, Marcela and Panowski, Siler H. and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {2}, pages = {284--295}, publisher = {Elsevier}, title = {{Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear integrity in postmitotic cells}}, doi = {10.1016/j.cell.2008.11.037}, volume = {136}, year = {2009}, } @article{7704, abstract = {Gradients of axon guidance molecules instruct the formation of continuous neural maps, such as the retinotopic map in the vertebrate visual system. Here we show that molecular gradients can also instruct the formation of a discrete neural map. In the fly olfactory system, axons of 50 classes of olfactory receptor neurons (ORNs) and dendrites of 50 classes of projection neurons (PNs) form one-to-one connections at discrete units called glomeruli. We provide expression, loss- and gain-of-function data to demonstrate that the levels of transmembrane Semaphorin-1a (Sema-1a), acting cell-autonomously as a receptor or part of a receptor complex, direct the dendritic targeting of PNs along the dorsolateral to ventromedial axis of the antennal lobe. Sema-1a also regulates PN axon targeting in higher olfactory centers. Thus, graded expression of Sema-1a contributes to connection specificity from ORNs to PNs and then to higher brain centers, ensuring proper representation of olfactory information in the brain.}, author = {Komiyama, Takaki and Sweeney, Lora Beatrice Jaeger and Schuldiner, Oren and Garcia, K. Christopher and Luo, Liqun}, issn = {0092-8674}, journal = {Cell}, number = {2}, pages = {399--410}, publisher = {Elsevier}, title = {{Graded expression of semaphorin-1a cell-autonomously directs dendritic targeting of olfactory projection neurons}}, doi = {10.1016/j.cell.2006.12.028}, volume = {128}, year = {2007}, }