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Journal of Cell Biology

Hsiang-Ting Hsu, Emily M Mace, Alexandre F Carisey, Dixita I Viswanath, Athanasia E Christakou, Martin Wiklund, Björn Önfelt, Jordan S Orange
Natural killer (NK) cell activation triggers sequential cellular events leading to destruction of diseased cells. We previously identified lytic granule convergence, a dynein- and integrin signal-dependent movement of lysosome-related organelles to the microtubule-organizing center, as an early step in the cell biological process underlying NK cell cytotoxicity. Why lytic granules converge during NK cell cytotoxicity, however, remains unclear. We experimentally controlled the availability of human ligands to regulate NK cell signaling and promote granule convergence with either directed or nondirected degranulation...
November 30, 2016: Journal of Cell Biology
Natalia Gomez-Navarro, Elizabeth Miller
Protein traffic is of critical importance for normal cellular physiology. In eukaryotes, spherical transport vesicles move proteins and lipids from one internal membrane-bound compartment to another within the secretory pathway. The process of directing each individual protein to a specific destination (known as protein sorting) is a crucial event that is intrinsically linked to vesicle biogenesis. In this review, we summarize the principles of cargo sorting by the vesicle traffic machinery and consider the diverse mechanisms by which cargo proteins are selected and captured into different transport vesicles...
November 30, 2016: Journal of Cell Biology
Babykumari Chitramuthu, Andrew Bateman
Progranulin is a secreted protein with roles in tumorigenesis, inflammation, and neurobiology, but its signaling receptors have remained unclear. In this issue, Neill et al. (2016. J. Cell Biol identify the tyrosine kinase EphA2 as a strong candidate for such a receptor, providing insight into progranulin and EphA2 signaling.
November 30, 2016: Journal of Cell Biology
Shun-Ichi Yamashita, Xiulian Jin, Kentaro Furukawa, Maho Hamasaki, Akiko Nezu, Hidenori Otera, Tetsu Saigusa, Tamotsu Yoshimori, Yasuyoshi Sakai, Katsuyoshi Mihara, Tomotake Kanki
Mitophagy is thought to play an important role in mitochondrial quality control. Mitochondrial division is believed to occur first, and autophagosome formation subsequently occurs to enwrap mitochondria as a process of mitophagy. However, there has not been any temporal analysis of mitochondrial division and autophagosome formation in mitophagy. Therefore, the relationships among these processes remain unclear. We show that the mitochondrial division factor Dnm1 in yeast or Drp1 in mammalian cells is dispensable for mitophagy...
November 30, 2016: Journal of Cell Biology
Thomas Neill, Simone Buraschi, Atul Goyal, Catherine Sharpe, Elizabeth Natkanski, Liliana Schaefer, Andrea Morrione, Renato V Iozzo
Although the growth factor progranulin was discovered more than two decades ago, the functional receptor remains elusive. Here, we discovered that EphA2, a member of the large family of Ephrin receptor tyrosine kinases, is a functional signaling receptor for progranulin. Recombinant progranulin bound with high affinity to EphA2 in both solid phase and solution. Interaction of progranulin with EphA2 caused prolonged activation of the receptor, downstream stimulation of mitogen-activated protein kinase and Akt, and promotion of capillary morphogenesis...
November 30, 2016: Journal of Cell Biology
Martin Graef
Whether or not mitophagy depends on prior mitochondrial fragmentation by the canonical mitochondrial division machinery is controversial. In this issue, Yamashita et al. (2016. J. Cell Biol. report that mitochondrial fragments start to bud and divide from mitochondrial tubules when in tight association with forming autophagosomes, but independently of the mitochondrial division factor Drp1/Dnm1.
November 30, 2016: Journal of Cell Biology
Ariadne Vlahakis, Nerea Lopez Muniozguren, Ted Powers
Autophagy is a catabolic process that recycles cytoplasmic contents and is crucial for cell survival during stress. The target of rapamycin (TOR) kinase regulates autophagy as part of two distinct protein complexes, TORC1 and TORC2. TORC1 negatively regulates autophagy according to nitrogen availability. In contrast, TORC2 functions as a positive regulator of autophagy during amino acid starvation, via its target kinase Ypk1, by repressing the activity of the calcium-dependent phosphatase calcineurin and promoting the general amino acid control (GAAC) response...
November 29, 2016: Journal of Cell Biology
Sascha Martens
The ATG8 family LC3/GABARAP proteins are attached to the membrane of nascent autophagosomes, but their functions during autophagy are unclear. In this issue, Nguyen et al. (2016. J. Cell Biol. show that LC3/GABARAP proteins are not essential for autophagosome formation but are critical for autophagosome-lysosome fusion.
November 25, 2016: Journal of Cell Biology
Ben Short
No abstract text is available yet for this article.
November 25, 2016: Journal of Cell Biology
Melina Casadio
No abstract text is available yet for this article.
November 25, 2016: Journal of Cell Biology
Gun-Hee Lee, Morihisa Fujita, Katsuyoshi Takaoka, Yoshiko Murakami, Yoshitaka Fujihara, Noriyuki Kanzawa, Kei-Ichi Murakami, Eriko Kajikawa, Yoko Takada, Kazunobu Saito, Masahito Ikawa, Hiroshi Hamada, Yusuke Maeda, Taroh Kinoshita
Glycosylphosphatidylinositol-anchored proteins (GPI-APs) can be shed from the cell membrane by GPI cleavage. In this study, we report a novel GPI-processing enzyme, termed post-glycosylphosphatidylinositol attachment to proteins 6 (PGAP6), which is a GPI-specific phospholipase A2 mainly localized at the cell surface. CRIPTO, a GPI-AP, which plays critical roles in early embryonic development by acting as a Nodal coreceptor, is a highly sensitive substrate of PGAP6, whereas CRYPTIC, a close homologue of CRIPTO, is not sensitive...
November 23, 2016: Journal of Cell Biology
Shweta Bendre, Arnaud Rondelet, Conrad Hall, Nadine Schmidt, Yu-Chih Lin, Gary J Brouhard, Alexander W Bird
The dynamic regulation of microtubules (MTs) during mitosis is critical for accurate chromosome segregation and genome stability. Cancer cell lines with hyperstabilized kinetochore MTs have increased segregation errors and elevated chromosomal instability (CIN), but the genetic defects responsible remain largely unknown. The MT depolymerase MCAK (mitotic centromere-associated kinesin) can influence CIN through its impact on MT stability, but how its potent activity is controlled in cells remains unclear. In this study, we show that GTSE1, a protein found overexpressed in aneuploid cancer cell lines and tumors, regulates MT stability during mitosis by inhibiting MCAK MT depolymerase activity...
November 23, 2016: Journal of Cell Biology
Christian Henneberger, Christian Steinhäuser
Astrocytes have been implicated in epilepsy development, but their contribution is under debate. In this issue, Shen et al. (2016. J. Cell Biol. demonstrate that early postnatal inflammatory stimuli activate toll-like receptor 4 signaling in astrocytes and promote excitatory synaptogenesis, thereby increasing seizure susceptibility in young and adult mice.
November 23, 2016: Journal of Cell Biology
Luke E Formosa, Michael T Ryan
In this issue, Qi et al. (2016. J. Cell Biol provide structural insights into the mechanisms of mitochondrial outer membrane fusion by investigating the structure of mitofusin 1 (MFN1). This work proposes a new model to explain the important and elusive process of MFN-mediated mitochondrial fusion.
November 23, 2016: Journal of Cell Biology
Isma Bennabi, Marie-Emilie Terret, Marie-Hélène Verlhac
Oocytes accumulate maternal stores (proteins, mRNAs, metabolites, etc.) during their growth in the ovary to support development after fertilization. To preserve this cytoplasmic maternal inheritance, they accomplish the difficult task of partitioning their cytoplasm unequally while dividing their chromosomes equally. Added to this complexity, most oocytes, for reasons still speculative, lack the major microtubule organizing centers that most cells use to assemble and position their spindles, namely canonical centrosomes...
November 22, 2016: Journal of Cell Biology
Jong Kook Park, Han Peng, Julia Katsnelson, Wending Yang, Nihal Kaplan, Ying Dong, Joshua Z Rappoport, CongCong He, Robert M Lavker
Macropinocytosis, by which cells ingest large amounts of fluid, and autophagy, the lysosome-based catabolic process, involve vesicular biogenesis (early stage) and turnover (end stage). Much is known about early-stage events; however, our understanding of how the end stages of these processes are governed is incomplete. Here we demonstrate that the microRNA-103/107(miR-103/107) family, which is preferentially expressed in the stem cell-enriched limbal epithelium, coordinately regulates aspects of both these activities...
November 21, 2016: Journal of Cell Biology
Thanh Ngoc Nguyen, Benjamin Scott Padman, Joanne Usher, Viola Oorschot, Georg Ramm, Michael Lazarou
Members of the Atg8 family of proteins are conjugated to autophagosomal membranes, where they have been proposed to drive autophagosome formation and selective sequestration of cargo. In mammals, the Atg8 family consists of six members divided into the LC3 and GABARAP subfamilies. To define Atg8 function, we used genome editing to generate knockouts of the LC3 and GABARAP subfamilies as well as all six Atg8 family members in HeLa cells. We show that Atg8s are dispensable for autophagosome formation and selective engulfment of mitochondria, but essential for autophagosome-lysosome fusion...
November 18, 2016: Journal of Cell Biology
Andrew T Schiffmacher, Vivien Xie, Lisa A Taneyhill
During epithelial-to-mesenchymal transitions (EMTs), cells disassemble cadherin-based junctions to segregate from the epithelia. Chick premigratory cranial neural crest cells reduce Cadherin-6B (Cad6B) levels through several mechanisms, including proteolysis, to permit their EMT and migration. Serial processing of Cad6B by a disintegrin and metalloproteinase (ADAM) proteins and γ-secretase generates intracellular C-terminal fragments (CTF2s) that could acquire additional functions. Here we report that Cad6B CTF2 possesses a novel pro-EMT role by up-regulating EMT effector genes in vivo...
November 17, 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
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