BIK ubiquitination by the E3 ligase Cul5-ASB11 determines cell fate during cellular stress
The BH3-only pro-apoptotic protein BIK is regulated by the ubiquitin–proteasome system. However, the mechanism of this regulation and its physiological functions remain elusive. Here, we identify Cul5-ASB11 as the E3 ligase targeting BIK for ubiquitination and degradation. ER stress leads to the activation of ASB11 by XBP1s during the adaptive phase of the unfolded protein response, which stimulates BIK ubiquitination, interaction with p97/VCP, and proteolysis. This mechanism of BIK degradation contributes to ER stress adaptation by promoting cell survival. Conversely, genotoxic agents down-regulate this IRE1α&...
Source: Journal of Cell Biology - September 1, 2019 Category: Cytology Authors: Chen, F.-Y., Huang, M.-Y., Lin, Y.-M., Ho, C.-H., Lin, S.-Y., Chen, H.-Y., Hung, M.-C., Chen, R.-H. Tags: Cell Death and Autophagy, Cell Signaling, Biochemistry, Cancer Articles Source Type: research
Hook3 is a scaffold for the opposite-polarity microtubule-based motors cytoplasmic dynein-1 and KIF1C
The unidirectional and opposite-polarity microtubule-based motors, dynein and kinesin, drive long-distance intracellular cargo transport. Cellular observations suggest that opposite-polarity motors may be coupled. We recently identified an interaction between the cytoplasmic dynein-1 activating adaptor Hook3 and the kinesin-3 KIF1C. Here, using in vitro reconstitutions with purified components, we show that KIF1C and dynein/dynactin can exist in a complex scaffolded by Hook3. Full-length Hook3 binds to and activates dynein/dynactin motility. Hook3 also binds to a short region in the "tail" of KIF1C, but unlike dynein/dynac...
Source: Journal of Cell Biology - September 1, 2019 Category: Cytology Authors: Kendrick, A. A., Dickey, A. M., Redwine, W. B., Tran, P. T., Vaites, L. P., Dzieciatkowska, M., Harper, J. W., Reck-Peterson, S. L. Tags: Cytoskeleton, Biochemistry, Biophysics Articles Source Type: research
Imaging within single NPCs reveals NXF1s role in mRNA export on the cytoplasmic side of the pore
Translocation of mRNA through the nuclear pore complex (NPC) requires interactions with different NPC regions. To determine the interactions that are crucial for effective mRNA export in living cells, we examined mRNA export within individual pores by applying various types of mRNA export blocks that stalled mRNPs at different stages of transition. Focusing on the major mRNA export factor NXF1, we found that initial mRNP binding to the NPC did not require NXF1 in the NPC, whereas release into the cytoplasm did. NXF1 localization in the NPC did not require RNA or RNA binding. Superresolution microscopy showed that NXF1 cons...
Source: Journal of Cell Biology - September 1, 2019 Category: Cytology Authors: Ben-Yishay, R., Mor, A., Shraga, A., Ashkenazy-Titelman, A., Kinor, N., Schwed-Gross, A., Jacob, A., Kozer, N., Kumar, P., Garini, Y., Shav-Tal, Y. Tags: RNA Biology Articles Source Type: research
Chromatin targeting of nuclear pore proteins induces chromatin decondensation
Nuclear pore complexes have emerged in recent years as chromatin-binding nuclear scaffolds, able to influence target gene expression. However, how nucleoporins (Nups) exert this control remains poorly understood. Here we show that ectopically tethering Drosophila Nups, especially Sec13, to chromatin is sufficient to induce chromatin decondensation. This decondensation is mediated through chromatin-remodeling complex PBAP, as PBAP is both robustly recruited by Sec13 and required for Sec13-induced decondensation. This phenomenon is not correlated with localization of the target locus to the nuclear periphery, but is correlat...
Source: Journal of Cell Biology - September 1, 2019 Category: Cytology Authors: Kuhn, T. M., Pascual-Garcia, P., Gozalo, A., Little, S. C., Capelson, M. Tags: Chromatin or Epigenetics, Development, Genetics Articles Source Type: research
Chromatin compartment dynamics in a haploinsufficient model of cardiac laminopathy
Mutations in A-type nuclear lamins cause dilated cardiomyopathy, which is postulated to result from dysregulated gene expression due to changes in chromatin organization into active and inactive compartments. To test this, we performed genome-wide chromosome conformation analyses in human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CMs) with a haploinsufficient mutation for lamin A/C. Compared with gene-corrected cells, mutant hiPSC-CMs have marked electrophysiological and contractile alterations, with modest gene expression changes. While large-scale changes in chromosomal topology are evident, diffe...
Source: Journal of Cell Biology - September 1, 2019 Category: Cytology Authors: Bertero, A., Fields, P. A., Smith, A. S. T., Leonard, A., Beussman, K., Sniadecki, N. J., Kim, D.-H., Tse, H.-F., Pabon, L., Shendure, J., Noble, W. S., Murry, C. E. Tags: Disease, Chromatin or Epigenetics, DNA Biology, Genetics Articles Source Type: research
CDK2 regulates the NRF1/Ehmt1 axis during meiotic prophase I
Meiosis generates four genetically distinct haploid gametes over the course of two reductional cell divisions. Meiotic divisions are characterized by the coordinated deposition and removal of various epigenetic marks. Here we propose that nuclear respiratory factor 1 (NRF1) regulates transcription of euchromatic histone methyltransferase 1 (EHMT1) to ensure normal patterns of H3K9 methylation during meiotic prophase I. We demonstrate that cyclin-dependent kinase (CDK2) can bind to the promoters of a number of genes in male germ cells including that of Ehmt1 through interaction with the NRF1 transcription factor. Our data i...
Source: Journal of Cell Biology - September 1, 2019 Category: Cytology Authors: Palmer, N., Talib, S. Z. A., Ratnacaram, C. K., Low, D., Bisteau, X., Lee, J. H. S., Pfeiffenberger, E., Wollmann, H., Tan, J. H. L., Wee, S., Sobota, R., Gunaratne, J., Messerschmidt, D. M., Guccione, E., Kaldis, P. Tags: Cell Cycle and Division, Genetics Articles Source Type: research
Coordinated internodal and paranodal adhesion controls accurate myelination by oligodendrocytes
Oligodendrocyte–axon contact is mediated by several cell adhesion molecules (CAMs) that are positioned at distinct sites along the myelin unit, yet their role during myelination remains unclear. Cadm4 and its axonal receptors, Cadm2 and Cadm3, as well as myelin-associated glycoprotein (MAG), are enriched at the internodes below the compact myelin, whereas NF155, which binds the axonal Caspr/contactin complex, is located at the paranodal junction that is formed between the axon and the terminal loops of the myelin sheath. Here we report that Cadm4-, MAG-, and Caspr-mediated adhesion cooperate during myelin membrane en...
Source: Journal of Cell Biology - September 1, 2019 Category: Cytology Authors: Elazar, N., Vainshtein, A., Rechav, K., Tsoory, M., Eshed-Eisenbach, Y., Peles, E. Tags: Adhesion, Neuroscience Reports Source Type: research
A bipartite sorting signal ensures specificity of retromer complex in membrane protein recycling
Retromer is an evolutionarily conserved protein complex, which sorts functionally diverse membrane proteins into recycling tubules/vesicles from the endosome. Many of the identified cargos possess a recycling signal sequence defined as ØX[L/M/V], where Ø is F/Y/W. However, this sequence is present in almost all proteins encoded in the genome. Also, several identified recycling sequences do not follow this rule. How then does retromer precisely select its cargos? Here, we reveal that an additional motif is also required for cargo retrieval. The two distinct motifs form a bipartite recycling signal recognized b...
Source: Journal of Cell Biology - September 1, 2019 Category: Cytology Authors: Suzuki, S. W., Chuang, Y.-S., Li, M., Seaman, M. N. J., Emr, S. D. Tags: Trafficking, Biochemistry Reports Source Type: research
Basal CHK1 activity safeguards its stability to maintain intrinsic S-phase checkpoint functions
The DNA replication machinery frequently encounters impediments that slow replication fork progression and threaten timely and error-free replication. The CHK1 protein kinase is essential to deal with replication stress (RS) and ensure genome integrity and cell survival, yet how basal levels and activity of CHK1 are maintained under physiological, unstressed conditions is not well understood. Here, we reveal that CHK1 stability is controlled by its steady-state activity during unchallenged cell proliferation. This autoactivatory mechanism, which depends on ATR and its coactivator ETAA1 and is tightly associated with CHK1 a...
Source: Journal of Cell Biology - September 1, 2019 Category: Cytology Authors: Michelena, J., Gatti, M., Teloni, F., Imhof, R., Altmeyer, M. Tags: Cell Cycle and Division, DNA Biology, Cancer Reports Source Type: research
The molecular architecture of the meiotic spindle is remodeled during metaphase arrest in oocytes
Before fertilization, oocytes of most species undergo a long, natural arrest in metaphase. Before this, prometaphase I is also prolonged, due to late stable kinetochore–microtubule attachment. How oocytes stably maintain the dynamic spindle for hours during these periods is poorly understood. Here we report that the bipolar spindle changes its molecular architecture during the long prometaphase/metaphase I in Drosophila melanogaster oocytes. By generating transgenic flies expressing GFP-tagged spindle proteins, we found that 14 of 25 spindle proteins change their distribution in the bipolar spindle. Among them, micro...
Source: Journal of Cell Biology - September 1, 2019 Category: Cytology Authors: Costa, M. F. A., Ohkura, H. Tags: Cytoskeleton, Cell Cycle and Division, Development, Genetics Reports Source Type: research
Microtubule minus-end stability is dictated by the tubulin off-rate
Dynamic organization of microtubule minus ends is vital for the formation and maintenance of acentrosomal microtubule arrays. In vitro, both microtubule ends switch between phases of assembly and disassembly, a behavior called dynamic instability. Although minus ends grow slower, their lifetimes are similar to those of plus ends. The mechanisms underlying these distinct dynamics remain unknown. Here, we use an in vitro reconstitution approach to investigate minus-end dynamics. We find that minus-end lifetimes are not defined by the mean size of the protective GTP-tubulin cap. Rather, we conclude that the distinct tubulin o...
Source: Journal of Cell Biology - September 1, 2019 Category: Cytology Authors: Strothman, C., Farmer, V., Arpag, G., Rodgers, N., Podolski, M., Norris, S., Ohi, R., Zanic, M. Tags: Cytoskeleton, Biochemistry, Biophysics Reports Source Type: research
Direct observation of branching MT nucleation in living animal cells
Centrosome-mediated microtubule (MT) nucleation has been well characterized; however, numerous noncentrosomal MT nucleation mechanisms exist. The branching MT nucleation pathway envisages that the -tubulin ring complex (-TuRC) is recruited to MTs by the augmin complex to initiate nucleation of new MTs. While the pathway is well conserved at a molecular and functional level, branching MT nucleation by core constituents has never been directly observed in animal cells. Here, multicolor TIRF microscopy was applied to visualize and quantitatively define the entire process of branching MT nucleation in dividing Drosophila cells...
Source: Journal of Cell Biology - September 1, 2019 Category: Cytology Authors: Verma, V., Maresca, T. J. Tags: Cytoskeleton, Cell Cycle and Division Reports Source Type: research
Early Career Advisory Board
In 2019, JCB created an Early Career Advisory Board as part of our ongoing efforts to ensure that the journal is representative and responsive to the needs of the entire cell biology community. Our Early Career Advisory Board members... (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - September 1, 2019 Category: Cytology Tags: Editorial Source Type: research
Challenging the "chromatin hypothesis" of cardiac laminopathies with LMNA mutant iPS cells
Lamins A and C are intermediate filaments that provide structural support to the nuclear envelope and regulate gene expression. In this issue, Bertero et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201902117) report that although lamin A/C haploinsufficient cardiomyocytes show disease-associated phenotypes, those changes cannot be explained by alterations in chromatin compartmentalization. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - September 1, 2019 Category: Cytology Authors: Mozzetta, C., Tedesco, F. S. Tags: Spotlight Source Type: research
Healthy attachments: Cell adhesion molecules collectively control myelin integrity
Many cell adhesion molecules are present along myelinated axons and in myelinating glia, but functional interactions among these proteins have not been fully elucidated. In this issue, Elazar et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201906099) report that distinct adhesion proteins act in coordination to ensure accurate myelination. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - September 1, 2019 Category: Cytology Authors: Li, J., Monk, K. R. Tags: Spotlight Source Type: research
