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Journal of Cell Biology

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https://www.readbyqxmd.com/read/28336773/elks1-helps-neuronal-synapses-diversify
#1
Ben Short
Study reveals how neurons vary the properties of individual synapses by recruiting different Munc13 proteins to presynaptic active zones.
March 23, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28330939/chlamydia-preserves-the-mitochondrial-network-necessary-for-replication-via-microrna-dependent-inhibition-of-fission
#2
Suvagata Roy Chowdhury, Anastasija Reimer, Malvika Sharan, Vera Kozjak-Pavlovic, Ana Eulalio, Bhupesh K Prusty, Martin Fraunholz, Karthika Karunakaran, Thomas Rudel
Obligate intracellular bacteria such as Chlamydia trachomatis depend on metabolites of the host cell and thus protect their sole replication niche by interfering with the host cells' stress response. Here, we investigated the involvement of host microRNAs (miRNAs) in maintaining the viability of C. trachomatis-infected primary human cells. We identified miR-30c-5p as a prominently up-regulated miRNA required for the stable down-regulation of p53, a major suppressor of metabolite supply in C. trachomatis-infected cells...
March 22, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28330938/macrophages-micromanagers-of-antagonistic-signaling-nanoclusters
#3
Christian Eggeling, Simon J Davis
How cells integrate antagonistic receptor signaling events is enigmatic. Using superresolution optical microscopy, Lopes et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201608094) demonstrate the nanometer-scale molecular reorganization of antagonistic signaling receptors in macrophages, after engagement by the receptors of activating and inhibitory ligands. They propose that large-scale rearrangements of this type underpin decision-making by these cells.
March 22, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28330937/raft-based-sphingomyelin-interactions-revealed-by-new-fluorescent-sphingomyelin-analogs
#4
Masanao Kinoshita, Kenichi G N Suzuki, Nobuaki Matsumori, Misa Takada, Hikaru Ano, Kenichi Morigaki, Mitsuhiro Abe, Asami Makino, Toshihide Kobayashi, Koichiro M Hirosawa, Takahiro K Fujiwara, Akihiro Kusumi, Michio Murata
Sphingomyelin (SM) has been proposed to form cholesterol-dependent raft domains and sphingolipid domains in the plasma membrane (PM). How SM contributes to the formation and function of these domains remains unknown, primarily because of the scarcity of suitable fluorescent SM analogs. We developed new fluorescent SM analogs by conjugating a hydrophilic fluorophore to the SM choline headgroup without eliminating its positive charge, via a hydrophilic nonaethylene glycol linker. The new analogs behaved similarly to the native SM in terms of their partitioning behaviors in artificial liquid order-disorder phase-separated membranes and detergent-resistant PM preparations...
March 22, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28325809/the-rab7-effector-plekhm1-binds-arl8b-to-promote-cargo-traffic-to-lysosomes
#5
Rituraj Marwaha, Subhash B Arya, Divya Jagga, Harmeet Kaur, Amit Tuli, Mahak Sharma
Endocytic, autophagic, and phagocytic vesicles move on microtubule tracks to fuse with lysosomes. Small GTPases, such as Rab7 and Arl8b, recruit their downstream effectors to mediate this transport and fusion. However, the potential cross talk between these two GTPases is unclear. Here, we show that the Rab7 effector PLEKHM1 simultaneously binds Rab7 and Arl8b, bringing about clustering and fusion of late endosomes and lysosomes. We show that the N-terminal RUN domain of PLEKHM1 is necessary and sufficient for interaction with Arl8b and its subsequent localization to lysosomes...
March 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28325808/membrane-remodeling-during-embryonic-abscission-in-caenorhabditis-elegans
#6
Julia König, E B Frankel, Anjon Audhya, Thomas Müller-Reichert
Abscission is the final step of cytokinesis and results in the physical separation of two daughter cells. In this study, we conducted a time-resolved series of electron tomographic reconstructions to define the steps required for the first embryonic abscission in Caenorhabditis elegans Our findings indicate that membrane scission occurs on both sides of the midbody ring with random order and that completion of the scission process requires actomyosin-driven membrane remodeling, but not microtubules. Moreover, continuous membrane removal predominates during the late stages of cytokinesis, mediated by both dynamin and the ESCRT (endosomal sorting complex required for transport) machinery...
March 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28325807/tensin-links-energy-metabolism-to-extracellular-matrix-assembly
#7
Emmanuel Dornier, Jim C Norman
The regulation of integrin function is key to fundamental cellular processes, including cell migration and extracellular matrix (ECM) assembly. In this issue, Georgiadou et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201609066) report that the metabolic sensor adenosine monophosphate-activated protein kinase influences tensin production to regulate α5β1-integrin and fibrillar adhesion assembly and thus reveal an important connection between energy metabolism and ECM assembly.
March 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28320825/structure-of-the-rzz-complex-and-molecular-basis-of-its-interaction-with-spindly
#8
Shyamal Mosalaganti, Jenny Keller, Anika Altenfeld, Michael Winzker, Pascaline Rombaut, Michael Saur, Arsen Petrovic, Annemarie Wehenkel, Sabine Wohlgemuth, Franziska Müller, Stefano Maffini, Tanja Bange, Franz Herzog, Herbert Waldmann, Stefan Raunser, Andrea Musacchio
Kinetochores are macromolecular assemblies that connect chromosomes to spindle microtubules (MTs) during mitosis. The metazoan-specific ≈800-kD ROD-Zwilch-ZW10 (RZZ) complex builds a fibrous corona that assembles on mitotic kinetochores before MT attachment to promote chromosome alignment and robust spindle assembly checkpoint signaling. In this study, we combine biochemical reconstitutions, single-particle electron cryomicroscopy, cross-linking mass spectrometry, and structural modeling to build a complete model of human RZZ...
March 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28320824/molecular-mechanism-of-dynein-recruitment-to-kinetochores-by-the-rod-zw10-zwilch-complex-and-spindly
#9
José B Gama, Cláudia Pereira, Patrícia A Simões, Ricardo Celestino, Rita M Reis, Daniel J Barbosa, Helena R Pires, Cátia Carvalho, João Amorim, Ana X Carvalho, Dhanya K Cheerambathur, Reto Gassmann
The molecular motor dynein concentrates at the kinetochore region of mitotic chromosomes in animals to accelerate spindle microtubule capture and to control spindle checkpoint signaling. In this study, we describe the molecular mechanism used by the Rod-Zw10-Zwilch complex and the adaptor Spindly to recruit dynein to kinetochores in Caenorhabditis elegans embryos and human cells. We show that Rod's N-terminal β-propeller and the associated Zwilch subunit bind Spindly's C-terminal domain, and we identify a specific Zwilch mutant that abrogates Spindly and dynein recruitment in vivo and Spindly binding to a Rod β-propeller-Zwilch complex in vitro...
March 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28320823/dynein-at-kinetochores-making-the-connection
#10
Toni McHugh, Julie P I Welburn
Dynein removes the checkpoint proteins from kinetochores once chromosomes are bioriented. In this issue, Gama et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201610108) and Mosalaganti et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201611060) reveal the molecular basis for how dynein and its adaptor protein Spindly are recruited to the ROD-Zw10-Zwilch complex in the fibrous corona of unattached kinetochores.
March 20, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28314741/an-engineered-minimal-chromosomal-passenger-complex-reveals-a-role-for-incenp-sli15-spindle-association-in-chromosome-biorientation
#11
Sarah Fink, Kira Turnbull, Arshad Desai, Christopher S Campbell
The four-subunit chromosomal passenger complex (CPC), whose enzymatic subunit is Aurora B kinase, promotes chromosome biorientation by detaching incorrect kinetochore-microtubule attachments. In this study, we use a combination of truncations and artificial dimerization in budding yeast to define the minimal CPC elements essential for its biorientation function. We engineered a minimal CPC comprised of the dimerized last third of the kinase-activating Sli15/INCENP scaffold and the catalytic subunit Ipl1/Aurora B...
March 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28314740/dual-recognition-of-chromatin-and-microtubules-by-incenp-is-important-for-mitotic-progression
#12
Michael S Wheelock, David J Wynne, Boo Shan Tseng, Hironori Funabiki
The chromosomal passenger complex (CPC), composed of inner centromere protein (INCENP), Survivin, Borealin, and the kinase Aurora B, contributes to the activation of the mitotic checkpoint. The regulation of CPC function remains unclear. Here, we reveal that in addition to Survivin and Borealin, the single α-helix (SAH) domain of INCENP supports CPC localization to chromatin and the mitotic checkpoint. The INCENP SAH domain also mediates INCENP's microtubule binding, which is negatively regulated by Cyclin-dependent kinase-mediated phosphorylation of segments flanking the SAH domain...
March 17, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28298410/fus-inclusions-disrupt-rna-localization-by-sequestering-kinesin-1-and-inhibiting-microtubule-detyrosination
#13
Kyota Yasuda, Sarah F Clatterbuck-Soper, Meredith E Jackrel, James Shorter, Stavroula Mili
Cytoplasmic inclusions of the RNA-binding protein fused in sarcoma (FUS) represent one type of membraneless ribonucleoprotein compartment. Formation of FUS inclusions is promoted by amyotrophic lateral sclerosis (ALS)-linked mutations, but the cellular functions affected upon inclusion formation are poorly defined. In this study, we find that FUS inclusions lead to the mislocalization of specific RNAs from fibroblast cell protrusions and neuronal axons. This is mediated by recruitment of kinesin-1 mRNA and protein within FUS inclusions, leading to a loss of detyrosinated glutamate (Glu)-microtubules (MTs; Glu-MTs) and an inability to support the localization of RNAs at protrusions...
March 15, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28298409/neurons-eat-glutamate-to-stay-alive
#14
Sarah-Maria Fendt, Patrik Verstreken
Neurons are thought to primarily rely on glucose to fuel mitochondrial metabolism. In this issue, Divakaruni et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201612067) show that neurons are also happy to use glutamate. When neurons use this neurotransmitter, its concentration drops, thus protecting against glutamate-induced excitotoxic stress.
March 15, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28292851/new-insights-into-protein-secretion-tango1-runs-rings-around-the-copii-coat
#15
Benjamin S Glick
In this issue, Liu et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201611088) and Raote et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201608080) use super-resolution microscopy to visualize large COPII-coated endoplasmic reticulum (ER) export carriers. Rings of TANGO1 surround COPII, implicating TANGO1 in organizing ER exit sites and in regulating COPII coat dynamics and geometry.
March 14, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28289092/ampk-negatively-regulates-tensin-dependent-integrin-activity
#16
Maria Georgiadou, Johanna Lilja, Guillaume Jacquemet, Camilo Guzmán, Maria Rafaeva, Charlotte Alibert, Yan Yan, Pranshu Sahgal, Martina Lerche, Jean-Baptiste Manneville, Tomi P Mäkelä, Johanna Ivaska
Tight regulation of integrin activity is paramount for dynamic cellular functions such as cell matrix adhesion and mechanotransduction. Integrin activation is achieved through intracellular interactions at the integrin cytoplasmic tails and through integrin-ligand binding. In this study, we identify the metabolic sensor AMP-activated protein kinase (AMPK) as a β1-integrin inhibitor in fibroblasts. Loss of AMPK promotes β1-integrin activity, the formation of centrally located active β1-integrin- and tensin-rich mature fibrillar adhesions, and cell spreading...
March 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28289091/membrane-nanoclusters-of-fc%C3%AE-ri-segregate-from-inhibitory-sirp%C3%AE-upon-activation-of-human-macrophages
#17
Filipa B Lopes, Štefan Bálint, Salvatore Valvo, James H Felce, Edith M Hessel, Michael L Dustin, Daniel M Davis
Signal integration between activating Fc receptors and inhibitory signal regulatory protein α (SIRPα) controls macrophage phagocytosis. Here, using dual-color direct stochastic optical reconstruction microscopy, we report that Fcγ receptor I (FcγRI), FcγRII, and SIRPα are not homogeneously distributed at macrophage surfaces but are organized in discrete nanoclusters, with a mean radius of 71 ± 11 nm, 60 ± 6 nm, and 48 ± 3 nm, respectively. Nanoclusters of FcγRI, but not FcγRII, are constitutively associated with nanoclusters of SIRPα, within 62 ± 5 nm, mediated by the actin cytoskeleton...
March 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28289090/correction-elks1-localizes-the-synaptic-vesicle-priming-protein-bmunc13-2-to-a-specific-subset-of-active-zones
#18
Hiroshi Kawabe, Miso Mitkovski, Pascal S Kaeser, Johannes Hirrlinger, Felipe Opazo, Dennis Nestvogel, Stefan Kalla, Anna Fejtova, Sophie E Verrier, Simon R Bungers, Benjamin H Cooper, Frederique Varoqueaux, Yun Wang, Ralf B Nehring, Eckart D Gundelfinger, Christian Rosenmund, Silvio O Rizzoli, Thomas C Südhof, Jeong-Seop Rhee, Nils Brose
No abstract text is available yet for this article.
March 13, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28264915/structural-analysis-of-the-role-of-tpx2-in-branching-microtubule-nucleation
#19
Raymundo Alfaro-Aco, Akanksha Thawani, Sabine Petry
The mitotic spindle consists of microtubules (MTs), which are nucleated by the γ-tubulin ring complex (γ-TuRC). How the γ-TuRC gets activated at the right time and location remains elusive. Recently, it was uncovered that MTs nucleate from preexisting MTs within the mitotic spindle, which requires the protein TPX2, but the mechanism basis for TPX2 action is unknown. Here, we investigate the role of TPX2 in branching MT nucleation. We establish the domain organization of Xenopus laevis TPX2 and define the minimal TPX2 version that stimulates branching MT nucleation, which we find is unrelated to TPX2's ability to nucleate MTs in vitro...
March 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28264914/unique-spectral-signatures-of-the-nucleic-acid-dye-acridine-orange-can-distinguish-cell-death-by-apoptosis-and-necroptosis
#20
Jason R Plemel, Andrew V Caprariello, Michael B Keough, Tyler J Henry, Shigeki Tsutsui, Tak H Chu, Geert J Schenk, Roel Klaver, V Wee Yong, Peter K Stys
Cellular injury and death are ubiquitous features of disease, yet tools to detect them are limited and insensitive to subtle pathological changes. Acridine orange (AO), a nucleic acid dye with unique spectral properties, enables real-time measurement of RNA and DNA as proxies for cell viability during exposure to various noxious stimuli. This tool illuminates spectral signatures unique to various modes of cell death, such as cells undergoing apoptosis versus necrosis/necroptosis. This new approach also shows that cellular RNA decreases during necrotic, necroptotic, and apoptotic cell death caused by demyelinating, ischemic, and traumatic injuries, implying its involvement in a wide spectrum of tissue pathologies...
March 6, 2017: Journal of Cell Biology
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