journal
https://read.qxmd.com/read/38358349/alternative-mechanisms-of-notch-activation-by-partitioning-into-distinct-endosomal-domains
#1
JOURNAL ARTICLE
Hideyuki Shimizu, Samira Hosseini-Alghaderi, Simon A Woodcock, Martin Baron
Different membrane microdomain compositions provide unique environments that can regulate signaling receptor function. We identify microdomains on the endosome membrane of Drosophila endosomes, enriched in lipid-raft or clathrin/ESCRT-0, which are associated with Notch activation by distinct, ligand-independent mechanisms. Transfer of Notch between microdomains is regulated by Deltex and Suppressor of deltex ubiquitin ligases and is limited by a gate-keeper role for ESCRT complexes. Ubiquitination of Notch by Deltex recruits it to the clathrin/ESCRT-0 microdomain and enhances Notch activation by an ADAM10-independent/TRPML-dependent mechanism...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38358348/vps13c-regulates-phospho-rab10-mediated-lysosomal-function-in-human-dopaminergic-neurons
#2
JOURNAL ARTICLE
Leonie F Schrӧder, Wesley Peng, Ge Gao, Yvette C Wong, Michael Schwake, Dimitri Krainc
Loss-of-function mutations in VPS13C are linked to early-onset Parkinson's disease (PD). While VPS13C has been previously studied in non-neuronal cells, the neuronal role of VPS13C in disease-relevant human dopaminergic neurons has not been elucidated. Using live-cell microscopy, we investigated the role of VPS13C in regulating lysosomal dynamics and function in human iPSC-derived dopaminergic neurons. Loss of VPS13C in dopaminergic neurons disrupts lysosomal morphology and dynamics with increased inter-lysosomal contacts, leading to impaired lysosomal motility and cellular distribution, as well as defective lysosomal hydrolytic activity and acidification...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38334958/ras-g-domains-allosterically-contribute-to-the-recognition-of-lipid-headgroups-and-acyl-chains
#3
JOURNAL ARTICLE
Neha Arora, Huanwen Mu, Hong Liang, Wenting Zhao, Yong Zhou
Mutant RAS are major contributors to cancer and signal primarily from nanoclusters on the plasma membrane (PM). Their C-terminal membrane anchors are main features of membrane association. However, the same RAS isoform bound to different guanine nucleotides spatially segregate. Different RAS nanoclusters all enrich a phospholipid, phosphatidylserine (PS). These findings suggest more complex membrane interactions. Our electron microscopy-spatial analysis shows that wild-types, G12V mutants, and membrane anchors of isoforms HRAS, KRAS4A, and KRAS4B prefer distinct PS species...
May 6, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38393070/fer-like-iron-deficiency-induced-transcription-factor-fit-accumulates-in-nuclear-condensates
#4
JOURNAL ARTICLE
Ksenia Trofimov, Regina Gratz, Rumen Ivanov, Yvonne Stahl, Petra Bauer, Tzvetina Brumbarova
The functional importance of nuclear protein condensation remains often unclear. The bHLH FER-like iron deficiency-induced transcription factor (FIT) controls iron acquisition and growth in plants. Previously described C-terminal serine residues allow FIT to interact and form active transcription factor complexes with subgroup Ib bHLH factors such as bHLH039. FIT has lower nuclear mobility than mutant FITmSS271AA. Here, we show that FIT undergoes a light-inducible subnuclear partitioning into FIT nuclear bodies (NBs)...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38393069/bill-weis-1959-2023-pioneering-structural-biologist-and-biochemist-who-revolutionized-our-understanding-of-cell-adhesion-and-wnt-signaling
#5
JOURNAL ARTICLE
Mark Peifer, Alexander R Dunn
No abstract text is available yet for this article.
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38376465/tunable-dnmt1-degradation-reveals-dnmt1-dnmt3b-synergy-in-dna-methylation-and-genome-organization
#6
JOURNAL ARTICLE
Andrea Scelfo, Viviana Barra, Nezar Abdennur, George Spracklin, Florence Busato, Catalina Salinas-Luypaert, Elena Bonaiti, Guillaume Velasco, Frédéric Bonhomme, Anna Chipont, Andréa E Tijhuis, Diana C J Spierings, Coralie Guérin, Paola Arimondo, Claire Francastel, Floris Foijer, Jӧrg Tost, Leonid Mirny, Daniele Fachinetti
DNA methylation (DNAme) is a key epigenetic mark that regulates critical biological processes maintaining overall genome stability. Given its pleiotropic function, studies of DNAme dynamics are crucial, but currently available tools to interfere with DNAme have limitations and major cytotoxic side effects. Here, we present cell models that allow inducible and reversible DNAme modulation through DNMT1 depletion. By dynamically assessing whole genome and locus-specific effects of induced passive demethylation through cell divisions, we reveal a cooperative activity between DNMT1 and DNMT3B, but not of DNMT3A, to maintain and control DNAme...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38353656/local-monomer-levels-and-established-filaments-potentiate-non-muscle-myosin-2-assembly
#7
JOURNAL ARTICLE
Melissa A Quintanilla, Hiral Patel, Huini Wu, Kem A Sochacki, Shreya Chandrasekar, Matthew Akamatsu, Jeremy D Rotty, Farida Korobova, James E Bear, Justin W Taraska, Patrick W Oakes, Jordan R Beach
The ability to dynamically assemble contractile networks is required throughout cell physiology, yet direct biophysical mechanisms regulating non-muscle myosin 2 filament assembly in living cells are lacking. Here, we use a suite of dynamic, quantitative imaging approaches to identify deterministic factors that drive myosin filament appearance and amplification. We find that actin dynamics regulate myosin assembly, but that the static actin architecture plays a less clear role. Instead, remodeling of actin networks modulates the local myosin monomer levels and facilitates assembly through myosin:myosin-driven interactions...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38334983/apoe-traffics-to-astrocyte-lipid-droplets-and-modulates-triglyceride-saturation-and-droplet-size
#8
JOURNAL ARTICLE
Ian A Windham, Alex E Powers, Joey V Ragusa, E Diane Wallace, Maria Clara Zanellati, Victoria H Williams, Colby H Wagner, Kristen K White, Sarah Cohen
The E4 variant of APOE strongly predisposes individuals to late-onset Alzheimer's disease. We demonstrate that in response to lipogenesis, apolipoprotein E (APOE) in astrocytes can avoid translocation into the endoplasmic reticulum (ER) lumen and traffic to lipid droplets (LDs) via membrane bridges at ER-LD contacts. APOE knockdown promotes fewer, larger LDs after a fatty acid pulse, which contain more unsaturated triglyceride after fatty acid pulse-chase. This LD size phenotype was rescued by chimeric APOE that targets only LDs...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38329452/microtubule-binding-domains-in-katanin-p80-subunit-are-essential-for-severing-activity-in-c-elegans
#9
JOURNAL ARTICLE
Eva Beaumale, Lucie Van Hove, Lionel Pintard, Nicolas Joly
Microtubule-severing enzymes (MSEs), such as Katanin, Spastin, and Fidgetin play essential roles in cell division and neurogenesis. They damage the microtubule (MT) lattice, which can either destroy or amplify the MT cytoskeleton, depending on the cellular context. However, little is known about how they interact with their substrates. We have identified the microtubule-binding domains (MTBD) required for Katanin function in C. elegans. Katanin is a heterohexamer of dimers containing a catalytic subunit p60 and a regulatory subunit p80, both of which are essential for female meiotic spindle assembly...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38323936/light-sensitive-phosphorylation-regulates-retinal-impdh1-activity-and-filament-assembly
#10
JOURNAL ARTICLE
S John Calise, Audrey G O'Neill, Anika L Burrell, Miles S Dickinson, Josephine Molfino, Charlie Clarke, Joel Quispe, David Sokolov, Rubén M Buey, Justin M Kollman
Inosine monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme in guanosine triphosphate (GTP) synthesis and assembles into filaments in cells, which desensitizes the enzyme to feedback inhibition and boosts nucleotide production. The vertebrate retina expresses two splice variants IMPDH1(546) and IMPDH1(595). In bovine retinas, residue S477 is preferentially phosphorylated in the dark, but the effects on IMPDH1 activity and regulation are unclear. Here, we generated phosphomimetic mutants to investigate structural and functional consequences of S477 phosphorylation...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38319250/a-role-for-vps13-mediated-lipid-transfer-at-the-er-endosome-contact-site-in-escrt-mediated-sorting
#11
JOURNAL ARTICLE
Sho W Suzuki, Matthew West, Yichen Zhang, Jenny S Fan, Rachel T Roberts, Greg Odorizzi, Scott D Emr
Endosomes are specialized organelles that function in the secretory and endocytic protein sorting pathways. Endocytosed cell surface receptors and transporters destined for lysosomal degradation are sorted into intraluminal vesicles (ILVs) at endosomes by endosomal sorting complexes required for transport (ESCRT) proteins. The endosomes (multivesicular bodies, MVBs) then fuse with the lysosome. During endosomal maturation, the number of ILVs increases, but the size of endosomes does not decrease despite the consumption of the limiting membrane during ILV formation...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38315097/dna-combing-versus-dna-spreading-and-the-separation-of-sister-chromatids
#12
JOURNAL ARTICLE
Alice Meroni, Sophie E Wells, Carmen Fonseca, Arnab Ray Chaudhuri, Keith W Caldecott, Alessandro Vindigni
DNA combing and DNA spreading are two central approaches for studying DNA replication fork dynamics genome-wide at single-molecule resolution by distributing labeled genomic DNA on coverslips or slides for immunodetection. Perturbations in DNA replication fork dynamics can differentially affect either leading or lagging strand synthesis, for example, in instances where replication is blocked by a lesion or obstacle on only one of the two strands. Thus, we sought to investigate whether the DNA combing and/or spreading approaches are suitable for resolving adjacent sister chromatids during DNA replication, thereby enabling the detection of DNA replication dynamics within individual nascent strands...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38252080/sub-membrane-actin-rings-compartmentalize-the-plasma-membrane
#13
JOURNAL ARTICLE
Jakob Rentsch, Selle Bandstra, Batuhan Sezen, Philipp Sigrist, Francesca Bottanelli, Bettina Schmerl, Sarah Shoichet, Frank Noé, Mohsen Sadeghi, Helge Ewers
The compartmentalization of the plasma membrane (PM) is a fundamental feature of cells. The diffusivity of membrane proteins is significantly lower in biological than in artificial membranes. This is likely due to actin filaments, but assays to prove a direct dependence remain elusive. We recently showed that periodic actin rings in the neuronal axon initial segment (AIS) confine membrane protein motion between them. Still, the local enrichment of ion channels offers an alternative explanation. Here we show, using computational modeling, that in contrast to actin rings, ion channels in the AIS cannot mediate confinement...
April 1, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38393314/pc4-a-new-regulator-of-cyclin-d1-transcript-levels
#14
JOURNAL ARTICLE
Anne Fassl, Piotr Sicinski
The expression of cyclin proteins is tightly regulated during the cell cycle, to allow precise activation of cyclin-dependent kinases. In this issue, Pan et al. (https://doi.org/10.1083/jcb.202308066) identify an RNA-binding protein, PC4, as a regulator of cyclin D1 mRNA stability in hepatocellular carcinoma cells. This study provides a new mechanism regulating the levels of a key cell cycle protein, cyclin D1, in human cells.
March 4, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38386112/the-distinct-localization-of-cdc42-isoforms-is-responsible-for-their-specific-functions-during-migration
#15
JOURNAL ARTICLE
Yamini Ravichandran, Jan Hänisch, Kerren Murray, Vanessa Roca, Florent Dingli, Damarys Loew, Valentin Sabatet, Batiste Boëda, Theresia E Stradal, Sandrine Etienne-Manneville
The small G-protein CDC42 is an evolutionary conserved polarity protein and a key regulator of polarized cell functions, including directed cell migration. In vertebrates, alternative splicing gives rise to two CDC42 proteins: the ubiquitously expressed isoform (CDC42u) and the brain isoform (CDC42b), which only differ in their carboxy-terminal sequence, including the CAAX motif essential for their association with membranes. We show that these divergent sequences do not directly affect the range of CDC42's potential binding partners but indirectly influence CDC42-driven signaling by controlling the subcellular localization of the two isoforms...
March 4, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38381149/centriolar-appendages-evolve-into-the-inner-sheath-of-mammalian-flagella
#16
JOURNAL ARTICLE
Jinyi Chen, Mingxi Liu
The annulus, a septin-based structure in vertebrate sperm connecting the MP and PP, has unclear migration mechanics. In this issue, Hoque et al. (https://doi.org/10.1083/jcb.202307147) report that the CBY3/CIBAR1 complex ensures its precise positioning by regulating membrane properties.
March 4, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38353696/a-map1b-cortactin-tks5-axis-regulates-tnbc-invasion-and-tumorigenesis
#17
JOURNAL ARTICLE
Hiroki Inoue, Taku Kanda, Gakuto Hayashi, Ryota Munenaga, Masayuki Yoshida, Kana Hasegawa, Takuya Miyagawa, Yukiya Kurumada, Jumpei Hasegawa, Tomoyuki Wada, Motoi Horiuchi, Yasuhiro Yoshimatsu, Fumiko Itoh, Yuki Maemoto, Kohei Arasaki, Yuichi Wakana, Tetsuro Watabe, Hiromichi Matsushita, Hironori Harada, Mitsuo Tagaya
The microtubule-associated protein MAP1B has been implicated in axonal growth and brain development. We found that MAP1B is highly expressed in the most aggressive and deadliest breast cancer subtype, triple-negative breast cancer (TNBC), but not in other subtypes. Expression of MAP1B was found to be highly correlated with poor prognosis. Depletion of MAP1B in TNBC cells impairs cell migration and invasion concomitant with a defect in tumorigenesis. We found that MAP1B interacts with key components for invadopodia formation, cortactin, and Tks5, the latter of which is a PtdIns(3,4)P2-binding and scaffold protein that localizes to invadopodia...
March 4, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38349334/periodic-changes-of-cyclin-d1-mrna-stability-are-regulated-by-pc4-modifications-in-the-cell-cycle
#18
JOURNAL ARTICLE
Qimei Pan, Peng Luo, Kaishun Hu, Yuntan Qiu, Gaoyu Liu, Shijie Dai, Bokang Cui, Dong Yin, Chunmeng Shi
The cell cycle is a highly regulated process in which proteins involved in cell cycle progression exhibit periodic expression patterns, controlled by specific mechanisms such as transcription, translation, and degradation. However, the precise mechanisms underlying the oscillations of mRNA levels in cell cycle regulators are not fully understood. In this study, we observed that the stability of cyclin D1 (CCND1) mRNA fluctuates during the cell cycle, with increased stability during interphase and decreased stability during the M phase...
March 4, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38335010/regulation-of-proteostasis-and-innate-immunity-via-mitochondria-nuclear-communication
#19
JOURNAL ARTICLE
Sookyung Kim, Theresa R Ramalho, Cole M Haynes
Mitochondria are perhaps best known as the "powerhouse of the cell" for their role in ATP production required for numerous cellular activities. Mitochondria have emerged as an important signaling organelle. Here, we first focus on signaling pathways mediated by mitochondria-nuclear communication that promote protein homeostasis (proteostasis). We examine the mitochondrial unfolded protein response (UPRmt) in C. elegans, which is regulated by a transcription factor harboring both a mitochondrial- and nuclear-targeting sequence, the integrated stress response in mammals, as well as the regulation of chromatin by mitochondrial metabolites...
March 4, 2024: Journal of Cell Biology
https://read.qxmd.com/read/38329462/ifn%C3%AE-priming-for-death
#20
JOURNAL ARTICLE
James E Vince
TNF signaling does not result in cell death unless multiple inhibitory signals are overcome, which can be accomplished by simultaneous signaling through IFNγ. In this issue, Deng and colleagues (https://doi.org/10.1083/jcb.202305026) dissect the mechanisms by which IFNγ signaling combines with TNF to mediate cell death through caspase-8, discussed by James E. Vince.
March 4, 2024: Journal of Cell Biology
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