TGF{beta}-like DAF-7 acts as a systemic signal for autophagy regulation in C. elegans
In response to stress conditions, autophagy activity in multicellular organisms is systemically modulated to ensure maintenance of cellular homeostasis at an organismal level. Very little is known about the intercellular signals that elicit the long-range organism-wide autophagy response. Here we showed that during Caenorhabditis elegans development, loss of cuticle annular furrow collagens elicits autophagy in the hypodermis, intestine, and muscle. The cilia of sensory neurons with cuticle-localized endings are essential for triggering this systemic response. The TGFβ-like molecule DAF-7, which is secreted in part fr...
Source: Journal of Cell Biology - December 1, 2019 Category: Cytology Authors: Zhang, Y., Qi, L., Zhang, H. Tags: Cell Death and Autophagy, Development Reports Source Type: research
Regulation of MT dynamics via direct binding of an Abl family kinase
Abl family kinases are essential regulators of cell shape and movement. Genetic studies revealed functional interactions between Abl kinases and microtubules (MTs), but the mechanism by which Abl family kinases regulate MTs remains unclear. Here, we report that Abl2 directly binds to MTs and regulates MT behaviors. Abl2 uses its C-terminal half to bind MTs, an interaction mediated in part through electrostatic binding to tubulin C-terminal tails. Using purified proteins, we found that Abl2 binds growing MTs and promotes MT polymerization and stability. In cells, knockout of Abl2 significantly impairs MT growth, and this de...
Source: Journal of Cell Biology - December 1, 2019 Category: Cytology Authors: Hu, Y., Lyu, W., Lowery, L. A., Koleske, A. J. Tags: Cytoskeleton, Migration, Motility, Biochemistry Reports Source Type: research
Soluble tubulin is significantly enriched at mitotic centrosomes
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 &alp...
Source: Journal of Cell Biology - December 1, 2019 Category: Cytology Authors: Baumgart, J., Kirchner, M., Redemann, S., Bond, A., Woodruff, J., Verbavatz, J.-M., Jülicher, F., Müller-Reichert, T., Hyman, A. A., Brugues, J. Tags: Cytoskeleton, Biophysics Reports Source Type: research
The RNA export factor Mex67 functions as a mobile nucleoporin
The RNA export factor Mex67 is essential for the transport of mRNA through the nuclear pore complex (NPC) in yeast, but the molecular mechanism of this export process remains poorly understood. Here, we use quantitative fluorescence microscopy techniques in live budding yeast cells to investigate how Mex67 facilitates mRNA export. We show that Mex67 exhibits little interaction with mRNA in the nucleus and localizes to the NPC independently of mRNA, occupying a set of binding sites offered by FG repeats in the NPC. The ATPase Dbp5, which is thought to remove Mex67 from transcripts, does not affect the interaction of Mex67 w...
Source: Journal of Cell Biology - December 1, 2019 Category: Cytology Authors: Derrer, C. P., Mancini, R., Vallotton, P., Huet, S., Weis, K., Dultz, E. Tags: RNA Biology Reports Source Type: research
TFEB controls retromer expression in response to nutrient availability
Endosomal recycling maintains the cell surface abundance of nutrient transporters for nutrient uptake, but how the cell integrates nutrient availability with recycling is less well understood. Here, in studying the recycling of human glutamine transporters ASCT2 (SLC1A5), LAT1 (SLC7A5), SNAT1 (SLC38A1), and SNAT2 (SLC38A2), we establish that following amino acid restriction, the adaptive delivery of SNAT2 to the cell surface relies on retromer, a master conductor of endosomal recycling. Upon complete amino acid starvation or selective glutamine depletion, we establish that retromer expression is upregulated by transcriptio...
Source: Journal of Cell Biology - December 1, 2019 Category: Cytology Authors: Curnock, R., Calcagni, A., Ballabio, A., Cullen, P. J. Tags: Cell Metabolism, Biochemistry Reports Source Type: research
Regulation of ETAA1-mediated ATR activation couples DNA replication fidelity and genome stability
The ATR kinase is a master regulator of the cellular response to DNA replication stress. Activation of ATR relies on dual pathways involving the TopBP1 and ETAA1 proteins, both of which harbor ATR-activating domains (AADs). However, the exact contribution of the recently discovered ETAA1 pathway to ATR signaling in different contexts remains poorly understood. Here, using an unbiased CRISPR-Cas9–based genome-scale screen, we show that the ATR-stimulating function of ETAA1 becomes indispensable for cell fitness and chromosome stability when the fidelity of DNA replication is compromised. We demonstrate that the ATR-ac...
Source: Journal of Cell Biology - December 1, 2019 Category: Cytology Authors: Achuthankutty, D., Thakur, R. S., Haahr, P., Hoffmann, S., Drainas, A. P., Bizard, A. H., Weischenfeldt, J., Hickson, I. D., Mailand, N. Tags: Cell Cycle and Division, DNA Biology Reports Source Type: research
Delineating the contribution of Spc105-bound PP1 to spindle checkpoint silencing and kinetochore microtubule attachment regulation
Accurate chromosome segregation during cell division requires the spindle assembly checkpoint (SAC), which detects unattached kinetochores, and an error correction mechanism that destabilizes incorrect kinetochore–microtubule attachments. While the SAC and error correction are both regulated by protein phosphatase 1 (PP1), which silences the SAC and stabilizes kinetochore–microtubule attachments, how these distinct PP1 functions are coordinated remains unclear. Here, we investigate the contribution of PP1, docked on its conserved kinetochore receptor Spc105/Knl1, to SAC silencing and attachment regulation. We f...
Source: Journal of Cell Biology - December 1, 2019 Category: Cytology Authors: Roy, B., Verma, V., Sim, J., Fontan, A., Joglekar, A. P. Tags: Cell Cycle and Division, Biochemistry Reports Source Type: research
Borealin-nucleosome interaction secures chromosome association of the chromosomal passenger complex
Chromosome association of the chromosomal passenger complex (CPC; consisting of Borealin, Survivin, INCENP, and the Aurora B kinase) is essential to achieve error-free chromosome segregation during cell division. Hence, understanding the mechanisms driving the chromosome association of the CPC is of paramount importance. Here using a multifaceted approach, we show that the CPC binds nucleosomes through a multivalent interaction predominantly involving Borealin. Strikingly, Survivin, previously suggested to target the CPC to centromeres, failed to bind nucleosomes on its own and requires Borealin and INCENP for its binding....
Source: Journal of Cell Biology - December 1, 2019 Category: Cytology Authors: Abad, M. A., Ruppert, J. G., Buzuk, L., Wear, M., Zou, J., Webb, K. M., Kelly, D. A., Voigt, P., Rappsilber, J., Earnshaw, W. C., Jeyaprakash, A. A. Tags: Cell Cycle and Division, Chromatin or Epigenetics, Biochemistry Reports Source Type: research
The postmitotic midbody: Regulating polarity, stemness, and proliferation
Abscission, the final stage of cell division, requires well-orchestrated changes in endocytic trafficking, microtubule severing, actin clearance, and the physical sealing of the daughter cell membranes. These processes are highly regulated, and any missteps in localized membrane and cytoskeleton dynamics often lead to a delay or a failure in cell division. The midbody, a microtubule-rich structure that forms during cytokinesis, is a key regulator of abscission and appears to function as a signaling platform coordinating cytoskeleton and endosomal dynamics during the terminal stages of cell division. It was long thought tha...
Source: Journal of Cell Biology - December 1, 2019 Category: Cytology Authors: Peterman, E., Prekeris, R. Tags: Cell Cycle and Division Review Source Type: research
DNA replication and mitotic entry: A brake model for cell cycle progression
The core function of the cell cycle is to duplicate the genome and divide the duplicated DNA into two daughter cells. These processes need to be carefully coordinated, as cell division before DNA replication is complete leads to genome instability and cell death. Recent observations show that DNA replication, far from being only a consequence of cell cycle progression, plays a key role in coordinating cell cycle activities. DNA replication, through checkpoint kinase signaling, restricts the activity of cyclin-dependent kinases (CDKs) that promote cell division. The S/G2 transition is therefore emerging as a crucial regulat...
Source: Journal of Cell Biology - December 1, 2019 Category: Cytology Authors: Lemmens, B., Lindqvist, A. Tags: Cell Cycle and Division Review Source Type: research
A calcium message for Niemann-Pick type C
Calcium is a ubiquitous secondary messenger that is critical for cellular function. In the highlighted article, Tiscione et al. (2019. J. Cell. Biol. https://doi.org/10.1083/jcb.201903018) describe a link between lysosomal cholesterol storage, calcium distribution alterations, and neuronal morphology in the neurodegenerative disorder Niemann-Pick type C. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - December 1, 2019 Category: Cytology Authors: Cologna, S. M. Tags: Spotlight Source Type: research
Glial SIK3: A central player in ion and volume homeostasis in Drosophila peripheral nerves
The electrical properties of neuronal cells rely on gradients of ions across their membranes and the extracellular fluid (ECF) in which they are bathed. Little is known regarding how the ECF volume and content is maintained. In this issue, Li et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201907138) identify the kinase SIK3 in glia as a key signal transduction regulator in ion and volume homeostasis in Drosophila peripheral nerves. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - December 1, 2019 Category: Cytology Authors: Kahanovitch, U., Olsen, M. L. Tags: Cell Signaling, Biophysics, Development Spotlight Source Type: research
Getting under the skin: Cuticle damage elicits systemic autophagy response in C. elegans
In this issue, Zhang et al. (2019. J. Cell. Biol. https://doi.org/10.1083/jcb.201907196) describe a molecular mechanism by which cuticular damage in the nematode C. elegans leads to systemic induction of autophagy by signals propagated from sensory neurons via the TGF-β signaling pathway. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - December 1, 2019 Category: Cytology Authors: Kumsta, C., Hansen, M. Tags: Spotlight Source Type: research
ETAA1 ensures proper chromosome segregation: A matter of S phase or mitosis?
ETAA1 activates the master checkpoint kinase ATR. Bass and Cortez (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201810058) recently reported an intra-mitotic function of ETAA1 that safeguards chromosome stability. In this issue, Achuthankutty et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201905064) describe a mechanism controlling the ATR-activating potential of ETAA1 in S phase to preserve chromosome stability. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - December 1, 2019 Category: Cytology Authors: Gonzalez Besteiro, M. A., Gottifredi, V. Tags: Spotlight Source Type: research
Michael Lazarou: Building a body of research
Lazarou investigates the relationship between mitochondria and autophagy. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - December 1, 2019 Category: Cytology Authors: ODonnell, M. A. Tags: People & amp;amp; Ideas Source Type: research
