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Journal of Cell Biology

Sanchari Datta, Yang Liu, Hanaa Hariri, Jade Bowerman, W Mike Henne
Lipid droplets (LDs) are nutrient reservoirs used by cells to maintain homeostasis. Nascent droplets form on the endoplasmic reticulum (ER) and grow following an influx of exogenous fatty acids (FAs). The budding of LDs requires extensive ER-LD crosstalk, but how this is regulated remains poorly understood. Here, we show that sorting nexin protein Snx14, an ER-resident protein associated with the cerebellar ataxia SCAR20, localizes to ER-LD contacts following FA treatment, where it promotes LD maturation. Using proximity-based APEX technology and topological dissection, we show that Snx14 accumulates specifically at ER-LD contacts independently of Seipin, where it remains ER-anchored and binds LDs in trans...
February 14, 2019: Journal of Cell Biology
Markus Seibert, Marcus Krüger, Nikolaus A Watson, Onur Sen, John R Daum, Johan A Slotman, Thomas Braun, Adriaan B Houtsmuller, Gary J Gorbsky, Ralf Jacob, Michael Kracht, Jonathan M G Higgins, M Lienhard Schmitz
Faithful mitotic chromosome segregation is required for the maintenance of genomic stability. We discovered the phosphorylation of histone H2B at serine 6 (H2B S6ph) as a new chromatin modification site and found that this modification occurs during the early mitotic phases at inner centromeres and pericentromeric heterochromatin. This modification is directly mediated by cyclin B1-associated CDK1, and indirectly by Aurora B, and is antagonized by PP1-mediated dephosphorylation. H2B S6ph impairs chromatin binding of the histone chaperone SET (I2PP2A), which is important for mitotic fidelity...
February 14, 2019: Journal of Cell Biology
Enfu Hui
No abstract text is available yet for this article.
February 13, 2019: Journal of Cell Biology
Thomas E Bass, David Cortez
The ATR kinase controls cell cycle transitions and the DNA damage response. ATR activity is regulated through two ATR-activating proteins, ETAA1 and TOPBP1. To examine how each activator contributes to ATR signaling, we used quantitative mass spectrometry to identify changes in protein phosphorylation in ETAA1- or TOPBP1-deficient cells. We identified 724, 285, and 118 phosphosites to be regulated by TOPBP1, ETAA1, or both ATR activators, respectively. Gene ontology analysis of TOPBP1- and ETAA1-dependent phosphoproteins revealed TOPBP1 to be a primary ATR activator for replication stress, while ETAA1 regulates mitotic ATR signaling...
February 12, 2019: Journal of Cell Biology
Ryan L Hanson, Joshua R Porter, Eric Batchelor
In response to DNA damage, the transcription factor p53 accumulates in a series of pulses. While p53 dynamics play a critical role in regulating stress responses, how p53 pulsing affects target protein expression is not well understood. Recently, we showed that p53 pulses generate diversity in target mRNA expression dynamics; however, given that mRNA and protein expression are not necessarily well correlated, it remains to be determined how p53 pulses impact target protein expression. Using computational and experimental approaches, we show that target protein decay rates filter p53 pulses: Distinct target protein expression dynamics are generated depending on the relationship between p53 pulse frequency and target mRNA and protein stability...
February 11, 2019: Journal of Cell Biology
Colin E Delaney, Stephen P Methot, Micol Guidi, Iskra Katic, Susan M Gasser, Jan Padeken
The segregation of the genome into accessible euchromatin and histone H3K9-methylated heterochromatin helps silence repetitive elements and tissue-specific genes. In Caenorhabditis elegans , MET-2, the homologue of mammalian SETDB1, catalyzes H3K9me1 and me2, yet like SETDB1, its regulation is enigmatic. Contrary to the cytosolic enrichment of overexpressed MET-2, we show that endogenous MET-2 is nuclear throughout development, forming perinuclear foci in a cell cycle-dependent manner. Mass spectrometry identified two cofactors that bind MET-2: LIN-65, a highly unstructured protein, and ARLE-14, a conserved GTPase effector...
February 8, 2019: Journal of Cell Biology
Bailey A Koch, Hui Jin, Robert J Tomko, Hong-Guo Yu
The nucleus is enclosed by the inner nuclear membrane (INM) and the outer nuclear membrane (ONM). While the ONM is continuous with the endoplasmic reticulum (ER), the INM is independent and separates the nucleoplasm from the ER lumen. Turnover of ER proteins has been well characterized by the ER-associated protein degradation (ERAD) pathway, but very little is known about turnover of resident INM proteins. Here we show that the anaphase-promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase, regulates the degradation of Mps3, a conserved integral protein of the INM...
February 8, 2019: Journal of Cell Biology
Devon E Mason, Joseph M Collins, James H Dawahare, Trung Dung Nguyen, Yang Lin, Sherry L Voytik-Harbin, Pinar Zorlutuna, Mervin C Yoder, Joel D Boerckel
Cell migration initiates by traction generation through reciprocal actomyosin tension and focal adhesion reinforcement, but continued motility requires adaptive cytoskeletal remodeling and adhesion release. Here, we asked whether de novo gene expression contributes to this cytoskeletal feedback. We found that global inhibition of transcription or translation does not impair initial cell polarization or migration initiation, but causes eventual migratory arrest through excessive cytoskeletal tension and over-maturation of focal adhesions, tethering cells to their matrix...
February 8, 2019: Journal of Cell Biology
Maria Livia Sassano, Patrizia Agostinis
ER-Golgi contact sites regulate lipid homeostasis and trafficking across the trans-Golgi network. However, their molecular nature is elusive. In this issue, Venditti et al. (2019. J. Cell Biol and shine new light on the molecular determinants coupling lipid exchange and cargo exit with maintenance of ER-Golgi contacts.
February 7, 2019: Journal of Cell Biology
Cindy L Fonseca, Heidi L H Malaby, Leslie A Sepaniac, Whitney Martin, Candice Byers, Anne Czechanski, Dana Messinger, Mary Tang, Ryoma Ohi, Laura G Reinholdt, Jason Stumpff
Chromosome alignment at the equator of the mitotic spindle is a highly conserved step during cell division; however, its importance to genomic stability and cellular fitness is not understood. Normal mammalian somatic cells lacking KIF18A function complete cell division without aligning chromosomes. These alignment-deficient cells display normal chromosome copy numbers in vitro and in vivo, suggesting that chromosome alignment is largely dispensable for maintenance of euploidy. However, we find that loss of chromosome alignment leads to interchromosomal compaction defects during anaphase, abnormal organization of chromosomes into a single nucleus at mitotic exit, and the formation of micronuclei in vitro and in vivo...
February 7, 2019: Journal of Cell Biology
Ingrid E Adriaans, Angika Basant, Bas Ponsioen, Michael Glotzer, Susanne M A Lens
Cytokinesis begins upon anaphase onset. An early step involves local activation of the small GTPase RhoA, which triggers assembly of an actomyosin-based contractile ring at the equatorial cortex. Here, we delineated the contributions of PLK1 and Aurora B to RhoA activation and cytokinesis initiation in human cells. Knock-down of PRC1, which disrupts the spindle midzone, revealed the existence of two pathways that can initiate cleavage furrow ingression. One pathway depends on a well-organized spindle midzone and PLK1, while the other depends on Aurora B activity and centralspindlin at the equatorial cortex and can operate independently of PLK1...
February 6, 2019: Journal of Cell Biology
Mehmet E Karasu, Nora Bouftas, Scott Keeney, Katja Wassmann
Meiosis poses unique challenges because two rounds of chromosome segregation must be executed without intervening DNA replication. Mammalian cells express numerous temporally regulated cyclins, but how these proteins collaborate to control meiosis remains poorly understood. Here, we show that female mice genetically ablated for cyclin B3 are viable-indicating that the protein is dispensable for mitotic divisions-but are sterile. Mutant oocytes appear normal until metaphase I but then display a highly penetrant failure to transition to anaphase I...
February 5, 2019: Journal of Cell Biology
Ishier Raote, Vivek Malhotra
Palade's corpus placed small vesicles as the sole means to transport proteins across stable distinct compartments of the secretory pathway. We suggest that cargo, spatial organization of secretory compartments, and the timing of fission of cargo-filled containers dictate the design of transport intermediates that can be vesicles and transient direct tunnels.
February 4, 2019: Journal of Cell Biology
Ivan Yudushkin
The membrane lipid phosphatidylinositol-3,4-bisphosphate (PI(3,4)P2 ) is an important signaling effector, controlling both anabolic pathways and membrane trafficking. In this issue, Goulden et al. (2019. J. Cell Biol. report a new PI(3,4)P2 probe and show that plasma membrane PI(3,4)P2 is a product of PI(3,4,5)P3 dephosphorylation.
February 1, 2019: Journal of Cell Biology
Heidi L H Malaby, Megan E Dumas, Ryoma Ohi, Jason Stumpff
Mitotic kinesins must be regulated to ensure a precise balance of spindle forces and accurate segregation of chromosomes into daughter cells. Here, we demonstrate that kinesin-binding protein (KBP) reduces the activity of KIF18A and KIF15 during metaphase. Overexpression of KBP disrupts the movement and alignment of mitotic chromosomes and decreases spindle length, a combination of phenotypes observed in cells deficient for KIF18A and KIF15, respectively. We show through gliding filament and microtubule co-pelleting assays that KBP directly inhibits KIF18A and KIF15 motor activity by preventing microtubule binding...
February 1, 2019: Journal of Cell Biology
Munechika Sugihara, Daisuke Morito, Shiori Ainuki, Yoshinobu Hirano, Kazutoyo Ogino, Akira Kitamura, Hiromi Hirata, Kazuhiro Nagata
Mysterin, also known as RNF213, is an intracellular protein that forms large toroidal oligomers. Mysterin was originally identified in genetic studies of moyamoya disease (MMD), a rare cerebrovascular disorder of unknown etiology. While mysterin is known to exert ubiquitin ligase and putative mechanical ATPase activities with a RING finger domain and two adjacent AAA+ modules, its biological role is poorly understood. Here, we report that mysterin is targeted to lipid droplets (LDs), ubiquitous organelles specialized for neutral lipid storage, and markedly increases their abundance in cells...
January 31, 2019: Journal of Cell Biology
Victoria Riccio, Nicholas Demers, Rong Hua, Miluska Vissa, Derrick T Cheng, Amy Wong Strilchuk, Yuqing Wang, G Angus McQuibban, Peter Kijun Kim
The regulation of organelle abundance is critical for cell function and survival; however, the mechanisms responsible are not fully understood. In this study, we characterize a role of the deubiquitinating enzyme USP30 in peroxisome maintenance. Peroxisomes are highly dynamic, changing in abundance in response to metabolic stress. In our recent study identifying the role of USP30 in mitophagy, we observed USP30 to be localized to punctate structures resembling peroxisomes. We report here that USP30, best known as a mitophagy regulator, is also necessary for regulating pexophagy, the selective autophagic degradation of peroxisomes...
January 30, 2019: Journal of Cell Biology
Yoo Jin Park, Minna Woo
No abstract text is available yet for this article.
January 29, 2019: Journal of Cell Biology
Tatiana Alfonso-Pérez, Daniel Hayward, James Holder, Ulrike Gruneberg, Francis A Barr
Cyclin B-dependent kinase (CDK1-CCNB1) promotes entry into mitosis. Additionally, it inhibits mitotic exit by activating the spindle checkpoint. This latter role is mediated through phosphorylation of the checkpoint kinase MPS1 and other spindle checkpoint proteins. We find that CDK1-CCNB1 localizes to unattached kinetochores and like MPS1 is lost from these structures upon microtubule attachment. This suggests that CDK1-CCNB1 is an integral component and not only an upstream regulator of the spindle checkpoint pathway...
January 23, 2019: Journal of Cell Biology
Daniel Hayward, Tatiana Alfonso-Pérez, Michael J Cundell, Michael Hopkins, James Holder, James Bancroft, Lukas H Hutter, Bela Novak, Francis A Barr, Ulrike Gruneberg
Spindle checkpoint signaling is initiated by recruitment of the kinase MPS1 to unattached kinetochores during mitosis. We show that CDK1-CCNB1 and a counteracting phosphatase PP2A-B55 regulate the engagement of human MPS1 with unattached kinetochores by controlling the phosphorylation status of S281 in the kinetochore-binding domain. This regulation is essential for checkpoint signaling, since MPS1S281A is not recruited to unattached kinetochores and fails to support the recruitment of other checkpoint proteins...
January 23, 2019: Journal of Cell Biology
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