SGK regulates pH increase and cyclin B-Cdk1 activation to resume meiosis in starfish ovarian oocytes
Tight regulation of intracellular pH (pHi) is essential for biological processes. Fully grown oocytes, having a large nucleus called the germinal vesicle, arrest at meiotic prophase I. Upon hormonal stimulus, oocytes resume meiosis to become fertilizable. At this time, the pHi increases via Na+/H+ exchanger activity, although the regulation and function of this change remain obscure. Here, we show that in starfish oocytes, serum- and glucocorticoid-regulated kinase (SGK) is activated via PI3K/TORC2/PDK1 signaling after hormonal stimulus and that SGK is required for this pHi increase and cyclin B–Cdk1 activation. When...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Hosoda, E., Hiraoka, D., Hirohashi, N., Omi, S., Kishimoto, T., Chiba, K. Tags: Cell Cycle and Division, Cell Signaling, Development Articles Source Type: research
SGK phosphorylates Cdc25 and Myt1 to trigger cyclin B-Cdk1 activation at the meiotic G2/M transition
The kinase cyclin B–Cdk1 complex is a master regulator of M-phase in both mitosis and meiosis. At the G2/M transition, cyclin B–Cdk1 activation is initiated by a trigger that reverses the balance of activities between Cdc25 and Wee1/Myt1 and is further accelerated by autoregulatory loops. In somatic cell mitosis, this trigger was recently proposed to be the cyclin A–Cdk1/Plk1 axis. However, in the oocyte meiotic G2/M transition, in which hormonal stimuli induce cyclin B–Cdk1 activation, cyclin A–Cdk1 is nonessential and hence the trigger remains elusive. Here, we show that SGK directly phospho...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Hiraoka, D., Hosoda, E., Chiba, K., Kishimoto, T. Tags: Cell Cycle and Division, Cell Signaling Articles Source Type: research
Mammalian kinetochores count attached microtubules in a sensitive and switch-like manner
The spindle assembly checkpoint (SAC) prevents anaphase until all kinetochores attach to the spindle. Each mammalian kinetochore binds many microtubules, but how many attached microtubules are required to turn off the checkpoint, and how the kinetochore monitors microtubule numbers, are not known and are central to understanding SAC mechanisms and function. To address these questions, here we systematically tune and fix the fraction of Hec1 molecules capable of microtubule binding. We show that Hec1 molecules independently bind microtubules within single kinetochores, but that the kinetochore does not independently process...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Kuhn, J., Dumont, S. Tags: Cytoskeleton, Cell Cycle and Division, Biophysics Articles Source Type: research
Yorkie and JNK revert syncytial muscles into myoblasts during Org-1-dependent lineage reprogramming
Lineage reprogramming has received increased research attention since it was demonstrated that lineage-restricted transcription factors can be used in vitro for direct reprogramming. Recently, we reported that the ventral longitudinal musculature of the adult Drosophila heart arises in vivo by direct lineage reprogramming from larval alary muscles, a process that starts with the dedifferentiation and fragmentation of syncytial muscle cells into mononucleate myoblasts and depends on Org-1 (Drosophila Tbx1). Here, we shed light on the events occurring downstream of Org-1 in this first step of transdifferentiation and show th...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Schaub, C., Rose, M., Frasch, M. Tags: Cell Signaling, Development Reports Source Type: research
Cortical tethering of mitochondria by the anchor protein Mcp5 enables uniparental inheritance
During sexual reproduction in eukaryotes, processes such as active degradation and dilution of paternal mitochondria ensure maternal mitochondrial inheritance. In the isogamous organism fission yeast, we employed high-resolution fluorescence microscopy to visualize mitochondrial inheritance during meiosis by differentially labeling mitochondria of the two parental cells. Remarkably, mitochondria, and thereby mitochondrial DNA from the parental cells, did not mix upon zygote formation but remained segregated at the poles by attaching to clusters of the anchor protein Mcp5 via its coiled-coil domain. We observed that this te...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Chacko, L. A., Mehta, K., Ananthanarayanan, V. Tags: Organelles, Cell Cycle and Division Reports Source Type: research
Phosphoregulation of tropomyosin is crucial for actin cable turnover and division site placement
Tropomyosin is a coiled-coil actin binding protein key to the stability of actin filaments. In muscle cells, tropomyosin is subject to calcium regulation, but its regulation in nonmuscle cells is not understood. Here, we provide evidence that the fission yeast tropomyosin, Cdc8, is regulated by phosphorylation of a serine residue. Failure of phosphorylation leads to an increased number and stability of actin cables and causes misplacement of the division site in certain genetic backgrounds. Phosphorylation of Cdc8 weakens its interaction with actin filaments. Furthermore, we show through in vitro reconstitution that phosph...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Palani, S., Köster, D. V., Hatano, T., Kamnev, A., Kanamaru, T., Brooker, H. R., Hernandez-Fernaud, J. R., Jones, A. M. E., Millar, J. B. A., Mulvihill, D. P., Balasubramanian, M. K. Tags: Cell Cycle and Division, Biochemistry, Biophysics Reports Source Type: research
A theory of centriole duplication based on self-organized spatial pattern formation
In each cell cycle, centrioles are duplicated to produce a single copy of each preexisting centriole. At the onset of centriole duplication, the master regulator Polo-like kinase 4 (Plk4) undergoes a dynamic change in its spatial pattern around the preexisting centriole, forming a single duplication site. However, the significance and mechanisms of this pattern transition remain unknown. Using super-resolution imaging, we found that centriolar Plk4 exhibits periodic discrete patterns resembling pearl necklaces, frequently with single prominent foci. Mathematical modeling and simulations incorporating the self-organization ...
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Takao, D., Yamamoto, S., Kitagawa, D. Tags: Cytoskeleton, Cell Cycle and Division, Biophysics, Systems and Computational Biology Reports Source Type: research
Beware of thy neighbor: Senescent cancer cells feast on adjacent cells to persist
Chemotherapy-resistant tumor cells are responsible for poor patient outcome. In this issue, Tonnessen-Murray et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201904051) elegantly show that chemotherapy triggers macrophage-like features in surviving cancer cells, which in turn phagocyte normal and tumor cells alike to outlast dormancy and cause relapse. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Napoli, M., Flores, E. R. Tags: Spotlight Source Type: research
Drive, filter, and stick: A protein sorting conspiracy in photoreceptors
The sorting of proteins into different functional compartments is a fundamental cellular task. In this issue, Maza et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201906024) demonstrate that distinct protein populations are dynamically generated in specialized regions of photoreceptors via an interplay of protein-membrane affinity, impeded diffusion, and driven transport. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Brown, A. I., Koslover, E. F. Tags: Protein Homeostasis, Trafficking, Biophysics Spotlight Source Type: research
From a syncytium to mononucleate cells and back: Yki and JNK in symphony
Alary muscle syncytia in Drosophila larvae undergo a remarkable process of dedifferentiation into single cells that then fuse to become ventral longitudinal muscle in the adult. In this issue, Schaub et al. (2019. J. Cell Biol. https://doi.org/10.1083/jcb.201905048) identify the Hippo and JNK signaling pathways as key regulators of this process of developmental remodeling of cell fate. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: Chaturvedi, D., VijayRaghavan, K. Tags: Cell Cycle and Division, Development Spotlight Source Type: research
Kazuhiro Maeshima: Excitement under the microscope
Maeshima investigates the higher order structures and dynamics of chromatin. (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - November 3, 2019 Category: Cytology Authors: ODonnell, M. A. Tags: People & amp;amp; Ideas Source Type: research
Correction: The dynein adaptor Hook2 plays essential roles in mitotic progression and cytokinesis
Vol. 218, No. 3, March 4, 2019. 10.1083/jcb.201804183. The authors were recently alerted that some of the blot images used to generate Fig. 2 E were inaccurate and similar to images shown in Fig. 1... (Source: Journal of Cell Biology)
Source: Journal of Cell Biology - October 6, 2019 Category: Cytology Authors: Dwivedi, D., Kumari, A., Rathi, S., Mylavarapu, S. V. S., Sharma, M. Tags: Corrections Source Type: research
Perlecan regulates pericyte dynamics in the maintenance and repair of the blood-brain barrier
Ischemic stroke causes blood–brain barrier (BBB) breakdown due to significant damage to the integrity of BBB components. Recent studies have highlighted the importance of pericytes in the repair process of BBB functions triggered by PDGFRβ up-regulation. Here, we show that perlecan, a major heparan sulfate proteoglycan of basement membranes, aids in BBB maintenance and repair through pericyte interactions. Using a transient middle cerebral artery occlusion model, we found larger infarct volumes and more BBB leakage in conditional perlecan (Hspg2)-deficient (Hspg2–/–-TG) mice than in control mice. Con...
Source: Journal of Cell Biology - October 6, 2019 Category: Cytology Authors: Nakamura, K., Ikeuchi, T., Nara, K., Rhodes, C. S., Zhang, P., Chiba, Y., Kazuno, S., Miura, Y., Ago, T., Arikawa-Hirasawa, E., Mukouyama, Y.-s., Yamada, Y. Tags: Disease, Cell Signaling, Migration, Motility, Neuroscience Articles Source Type: research
Phosphorylation of CEP83 by TTBK2 is necessary for cilia initiation
Primary cilia are microtubule-based organelles that play important roles in development and tissue homeostasis. Tau-tubulin kinase-2 (TTBK2) is genetically linked to spinocerebellar ataxia type 11, and its kinase activity is crucial for ciliogenesis. Although it has been shown that TTBK2 is recruited to the centriole by distal appendage protein CEP164, little is known about TTBK2 substrates associated with its role in ciliogenesis. Here, we perform superresolution microscopy and discover that serum starvation results in TTBK2 redistribution from the periphery toward the root of distal appendages. Our biochemical analyses u...
Source: Journal of Cell Biology - October 6, 2019 Category: Cytology Authors: Lo, C.-H., Lin, I.-H., Yang, T. T., Huang, Y.-C., Tanos, B. E., Chou, P.-C., Chang, C.-W., Tsay, Y.-G., Liao, J.-C., Wang, W.-J. Tags: Cilia, Development Articles Source Type: research
YAP and TAZ regulate cell volume
How mammalian cells regulate their physical size is currently poorly understood, in part due to the difficulty in accurately quantifying cell volume in a high-throughput manner. Here, using the fluorescence exclusion method, we demonstrate that the mechanosensitive transcriptional regulators YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are regulators of single-cell volume. The role of YAP/TAZ in volume regulation must go beyond its influence on total cell cycle duration or cell shape to explain the observed changes in volume. Moreover, for our experimental conditions, volume reg...
Source: Journal of Cell Biology - October 6, 2019 Category: Cytology Authors: Perez-Gonzalez, N. A., Rochman, N. D., Yao, K., Tao, J., Le, M.-T. T., Flanary, S., Sablich, L., Toler, B., Crentsil, E., Takaesu, F., Lambrus, B., Huang, J., Fu, V., Chengappa, P., Jones, T. M., Holland, A. J., An, S., Wirtz, D., Petrie, R. J., Guan, K.- Tags: Cell Cycle and Division, Biophysics, Systems and Computational Biology Articles Source Type: research
