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Journal of Cell Biology

Amanda L Neisch, Thomas P Neufeld, Thomas S Hays
Autophagy plays an essential role in the cellular homeostasis of neurons, facilitating the clearance of cellular debris. This clearance process is orchestrated through the assembly, transport, and fusion of autophagosomes with lysosomes for degradation. The motor protein dynein drives autophagosome motility from distal sites of assembly to sites of lysosomal fusion. In this study, we identify the scaffold protein CKA (connector of kinase to AP-1) as essential for autophagosome transport in neurons. Together with other core components of the striatin-interacting phosphatase and kinase (STRIPAK) complex, we show that CKA associates with dynein and directly binds Atg8a, an autophagosomal protein...
January 18, 2017: Journal of Cell Biology
Daniel Cirera-Salinas, Jian Yu, Maxime Bodak, Richard P Ngondo, Kristina M Herbert, Constance Ciaudo
Mouse embryonic stem cells (mESCs) deficient for DGCR8, a key component of the microprocessor complex, present strong differentiation defects. However, the exact reasons impairing their commitment remain elusive. The analysis of newly generated mutant mESCs revealed that DGCR8 is essential for the exit from the pluripotency state. To dissociate canonical versus noncanonical functions of DGCR8, we complemented the mutant mESCs with a phosphomutant DGCR8, which restored microRNA levels but did not rescue the exit from pluripotency defect...
January 18, 2017: Journal of Cell Biology
Ayelén Mariana Distéfano, María Victoria Martin, Juan Pablo Córdoba, Andrés Martín Bellido, Sebastián D'Ippólito, Silvana Lorena Colman, Débora Soto, Juan Alfredo Roldán, Carlos Guillermo Bartoli, Eduardo Julián Zabaleta, Diego Fernando Fiol, Brent R Stockwell, Scott J Dixon, Gabriela Carolina Pagnussat
In plants, regulated cell death (RCD) plays critical roles during development and is essential for plant-specific responses to abiotic and biotic stresses. Ferroptosis is an iron-dependent, oxidative, nonapoptotic form of cell death recently described in animal cells. In animal cells, this process can be triggered by depletion of glutathione (GSH) and accumulation of lipid reactive oxygen species (ROS). We investigated whether a similar process could be relevant to cell death in plants. Remarkably, heat shock (HS)-induced RCD, but not reproductive or vascular development, was found to involve a ferroptosis-like cell death process...
January 18, 2017: Journal of Cell Biology
Benjamin Alleva, Nathan Balukoff, Amy Peiper, Sarit Smolikove
In meiotic prophase I, homologous chromosome pairing is promoted through chromosome movement mediated by nuclear envelope proteins, microtubules, and dynein. After proper homologue pairing has been established, the synaptonemal complex (SC) assembles along the paired homologues, stabilizing their interaction and allowing for crossing over to occur. Previous studies have shown that perturbing chromosome movement leads to pairing defects and SC polycomplex formation. We show that FKB-6 plays a role in SC assembly and is required for timely pairing and proper double-strand break repair kinetics...
January 11, 2017: Journal of Cell Biology
Bradlee Nelms, Natasha Furtado Dalomba, Wayne Lencer
Endosome transport by transcytosis is the primary mechanism by which proteins and other large cargo traverse epithelial barriers in normal tissue. Transcytosis is also essential for establishing and maintaining membrane polarity in epithelia and other polarized cells. To identify novel components of this pathway, we conducted a high-throughput RNA interference screen for factors necessary for the bidirectional transcytosis of IgG by the Fcγ receptor FcRn. This screen identified 23 genes whose suppression resulted in a reproducible decrease in FcRn-mediated transcytosis...
January 9, 2017: Journal of Cell Biology
Shuji Wakatsuki, Shinji Tokunaga, Megumi Shibata, Toshiyuki Araki
Macroautophagy is a catabolic process, in which portions of cytoplasm or organelles are delivered to lysosomes for degradation. Emerging evidence has indicated a pathological connection between axonal degeneration and autophagy. However, the physiological function and induction mechanism of autophagy in axons remain elusive. We herein show that, through activation of BECLIN1, glycogen synthase kinase 3B (GSK3B)-mediated phosphorylation of BCL2 family member MCL1 induces axonal autophagy and axonal degeneration...
January 4, 2017: Journal of Cell Biology
Sangkyun Cho, Jerome Irianto, Dennis E Discher
The nucleus is linked mechanically to the extracellular matrix via multiple polymers that transmit forces to the nuclear envelope and into the nuclear interior. Here, we review some of the emerging mechanisms of nuclear mechanosensing, which range from changes in protein conformation and transcription factor localization to chromosome reorganization and membrane dilation up to rupture. Nuclear mechanosensing encompasses biophysically complex pathways that often converge on the main structural proteins of the nucleus, the lamins...
January 2, 2017: Journal of Cell Biology
Oguzhan Atay, Jan M Skotheim
Mitogen-activated protein kinase (MAPK) pathways are conserved from yeast to man and regulate a variety of cellular processes, including proliferation and differentiation. Recent developments show how MAPK pathways perform exquisite spatial and temporal signal processing and underscores the importance of studying the dynamics of signaling pathways to understand their physiological response. The importance of dynamic mechanisms that process input signals into graded downstream responses has been demonstrated in the pheromone-induced and osmotic stress-induced MAPK pathways in yeast and in the mammalian extracellular signal-regulated kinase MAPK pathway...
January 2, 2017: Journal of Cell Biology
Simon D'Archivio, Bill Wickstead
Kinetochores are multiprotein complexes that couple eukaryotic chromosomes to the mitotic spindle to ensure proper segregation. The model for kinetochore assembly is conserved between humans and yeast, and homologues of several components are widely distributed in eukaryotes, but key components are absent in some lineages. The recent discovery in a lineage of protozoa called kinetoplastids of unconventional kinetochores with no apparent homology to model organisms suggests that more than one system for eukaryotic chromosome segregation may exist...
December 29, 2016: Journal of Cell Biology
Christine J Smoyer, Santharam S Katta, Jennifer M Gardner, Lynn Stoltz, Scott McCroskey, William D Bradford, Melainia McClain, Sarah E Smith, Brian D Slaughter, Jay R Unruh, Sue L Jaspersen
Understanding the protein composition of the inner nuclear membrane (INM) is fundamental to elucidating its role in normal nuclear function and in disease; however, few tools exist to examine the INM in living cells, and the INM-specific proteome remains poorly characterized. Here, we adapted split green fluorescent protein (split-GFP) to systematically localize known and predicted integral membrane proteins in Saccharomyces cerevisiae to the INM as opposed to the outer nuclear membrane. Our data suggest that components of the endoplasmic reticulum (ER) as well as other organelles are able to access the INM, particularly if they contain a small extraluminal domain...
November 9, 2016: Journal of Cell Biology
Xiaodong Fang, Jianying Luo, Ryuichi Nishihama, Carsten Wloka, Christopher Dravis, Mirko Travaglia, Masayuki Iwase, Elizabeth A Vallen, Erfei Bi
No abstract text is available yet for this article.
November 7, 2016: Journal of Cell Biology
Emmanuel Martin, Marie-Hélène Ouellette, Sarah Jenna
The antagonism between the GTPases Rac1 and RhoA controls cell-to-cell heterogeneity in isogenic populations of cells in vitro and epithelial morphogenesis in vivo Its involvement in the regulation of cell-to-cell heterogeneity during epidermal morphogenesis has, however, never been addressed. We used a quantitative cell imaging approach to characterize epidermal morphogenesis at a single-cell level during early elongation of Caenorhabditis elegans embryos. This study reveals that a Rac1-like pathway, involving the Rac/Cdc42 guanine-exchange factor β-PIX/PIX-1 and effector PAK1/PAK-1, and a RhoA-like pathway, involving ROCK/LET-502, control the remodeling of apical junctions and the formation of basolateral protrusions in distinct subsets of hypodermal cells...
November 7, 2016: Journal of Cell Biology
Jocelyn F Krey, Evan S Krystofiak, Rachel A Dumont, Sarath Vijayakumar, Dongseok Choi, Francisco Rivero, Bechara Kachar, Sherri M Jones, Peter G Barr-Gillespie
With their essential role in inner ear function, stereocilia of sensory hair cells demonstrate the importance of cellular actin protrusions. Actin packing in stereocilia is mediated by cross-linkers of the plastin, fascin, and espin families. Although mice lacking espin (ESPN) have no vestibular or auditory function, we found that mice that either lacked plastin 1 (PLS1) or had nonfunctional fascin 2 (FSCN2) had reduced inner ear function, with double-mutant mice most strongly affected. Targeted mass spectrometry indicated that PLS1 was the most abundant cross-linker in vestibular stereocilia and the second most abundant protein overall; ESPN only accounted for ∼15% of the total cross-linkers in bundles...
November 3, 2016: Journal of Cell Biology
Tamako Nishimura, Shoko Ito, Hiroko Saito, Sylvain Hiver, Kenta Shigetomi, Junichi Ikenouchi, Masatoshi Takeichi
Epithelial junctions comprise two subdomains, the apical junctional complex (AJC) and the adjacent lateral membrane contacts (LCs), that span the majority of the junction. The AJC is lined with circumferential actin cables, whereas the LCs are associated with less-organized actin filaments whose roles are elusive. We found that DAAM1, a formin family actin regulator, accumulated at the LCs, and its depletion caused dispersion of actin filaments at these sites while hardly affecting circumferential actin cables...
November 2, 2016: Journal of Cell Biology
Thomas N Gaitanos, Jorg Koerner, Ruediger Klein
No abstract text is available yet for this article.
October 31, 2016: Journal of Cell Biology
Marina Simian, Mina J Bissell
In the last ten years, there has been a dramatic surge in the number of publications where single or groups of cells are grown in substrata that have elements of basement membrane leading to the formation of tissue-like structures referred to as organoids. However, this field of research began many decades ago, when the pioneers of cell culture began to ask questions we still ask today: How does organogenesis occur? How do signals integrate to make such vastly different tissues and organs given that the sequence of the genome in our trillions of cells is identical? Here, we summarize how work over the past century generated the conceptual framework that has allowed us to make progress in the understanding of tissue-specific morphogenetic programs...
January 2, 2017: Journal of Cell Biology
Hitoshi Matakatsu, Seth S Blair, Richard G Fehon
The large protocadherin Fat functions to promote Hippo pathway activity in restricting tissue growth. Loss of Fat leads to accumulation of the atypical myosin Dachs at the apical junctional region, which in turn promotes growth by inhibiting Warts. We previously identified Approximated (App), a DHHC domain palmitoyltransferase, as a negative regulator of Fat signaling in growth control. We show here that App promotes growth by palmitoylating the intracellular domain of Fat, and that palmitoylation negatively regulates Fat function...
January 2, 2017: Journal of Cell Biology
Brooke J Bevis
The science universe is dimmer after one of our brightest stars, Susan Lee Lindquist, was taken by cancer on October 27, 2016. Sue was an innovative, creative, out-of-the-box scientific thinker. She had unique biological intuition-an instinct for both the way things worked and the right questions to ask to uncover new research insights. Her wide-ranging career began with the study of protein folding and molecular chaperones, and she went on to show that protein folding can have profound and unexpected biological effects on such diverse processes as cancer, evolution, and neurodegenerative disease...
January 2, 2017: Journal of Cell Biology
Alexander Benjamin Schendzielorz, Christian Schulz, Oleksandr Lytovchenko, Anne Clancy, Bernard Guiard, Raffaele Ieva, Martin van der Laan, Peter Rehling
Two driving forces energize precursor translocation across the inner mitochondrial membrane. Although the membrane potential (Δψ) is considered to drive translocation of positively charged presequences through the TIM23 complex (presequence translocase), the activity of the Hsp70-powered import motor is crucial for the translocation of the mature protein portion into the matrix. In this study, we show that mitochondrial matrix proteins display surprisingly different dependencies on the Δψ. However, a precursor's hypersensitivity to a reduction of the Δψ is not linked to the respective presequence, but rather to the mature portion of the polypeptide chain...
January 2, 2017: Journal of Cell Biology
Li-Ka Liu, Vineet Choudhary, Alexandre Toulmay, William A Prinz
Ceramides are key intermediates in sphingolipid biosynthesis and potent signaling molecules. However, excess ceramide is toxic, causing growth arrest and apoptosis. In this study, we identify a novel mechanism by which cells prevent the toxic accumulation of ceramides; they facilitate nonvesicular ceramide transfer from the endoplasmic reticulum (ER) to the Golgi complex, where ceramides are converted to complex sphingolipids. We find that the yeast protein Nvj2p promotes the nonvesicular transfer of ceramides from the ER to the Golgi complex...
January 2, 2017: Journal of Cell Biology
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