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Yuwei Jiang, Matthew D Berg, Julie Genereaux, Khadija Ahmed, Martin L Duennwald, Christopher J Brandl, Patrick Lajoie
Chromatin remodeling regulates gene expression in response to the accumulation of misfolded polyQ proteins associated with Huntington's disease (HD). Tra1 is an essential component of both the SAGA/SLIK and NuA4 transcription co-activator complexes and is linked to multiple cellular processes, including protein trafficking and signaling pathways associated with misfolded protein stress. Cells with compromised Tra1 activity display phenotypes distinct from deletions encoding components of the SAGA and NuA4 complexes, indicating a potentially unique regulatory role of Tra1 in the cellular response to protein misfolding...
February 10, 2019: Traffic
Mohit P Mathew, Julie G Donaldson
In contrast to clathrin mediated endocytosis (CME) which is well characterized and understood, little is known about the regulation and machinery underlying clathrin independent endocytosis (CIE). There is also a wide variation in the requirements each individual CIE cargo has for its internalization. Recent studies have shown that CIE is affected by glycosylation and glycan interactions. We briefly review these studies and explore how these studies mesh with one another. We then discuss what this sensitivity to glycan interactions could indicate for the regulation of CIE...
February 1, 2019: Traffic
Rachel E Turn, Ryan S D'Souza, Adam A Wall
In September 2018, conference organizers Nava Segev (University of Illinois, Chicago) and Marino Zerial (MPI, Dresden) hosted the 5th FASEB Meeting in Small GTPases in Membrane Processes: Trafficking, Autophagy, and Disease at the National Conference Center in Leesburg, Virginia. With over 100 attendees from across the globe sharing their varied expertise and interests, we came together with the common goal of gaining a better understanding of how small GTPases and their regulators act in both canonical and non-canonical pathways to conduct a diversity of essential cellular functions...
January 21, 2019: Traffic
Barbara Knoblach, Richard A Rachubinski
Organelle tethering and intercommunication are crucial for proper cell function. We previously described a tether between peroxisomes and the endoplasmic reticulum (ER) that acts in peroxisome population control in the yeast, Saccharomyces cerevisiae. Components of this tether are Pex3p, an integral membrane protein of both peroxisomes and the ER, and Inp1p, a connector that links peroxisomes to the ER. Here we report the analysis of random Inp1p mutants that enabled identification of regions in Inp1p required for the assembly and maintenance of the ER-peroxisome tether...
December 30, 2018: Traffic
Braden T Lobingier, Mark von Zastrow
G protein-coupled receptors (GPCRs) physically connect extracellular information with intracellular signal propagation. Membrane trafficking plays a supportive role by 'bookending' signaling events: movement through the secretory pathway delivers GPCRs to the cell surface where receptors can sample the extracellular environment, while endocytosis and endo-lysosomal membrane trafficking provide a versatile system to titrate cellular signaling potential and maintain homeostatic control. Recent evidence suggests that, in addition to these important effects, GPCR trafficking actively shapes the cellular signaling response by altering the location and timing of specific receptor-mediated signaling reactions...
December 22, 2018: Traffic
Jürgen Fritsch, Vladimir Tchikov, Lena Hennig, Ralph Lucius, Stefan Schütze
Homeostasis and the complex functions of organisms and cells rely on the sophisticated spatial and temporal regulation of signalling in different intra and extracellular compartments and via different mediators. We here present a set of fast and easy to use protocols for the target-specific immunomagnetic enrichment of receptor containing endosomes ('receptosomes'), plasma membranes, lysosomes and exosomes. Isolation of subcellular organelles and exosomes is prerequisite for and will advance their detailed subsequent biochemical and functional analysis...
December 20, 2018: Traffic
Zhe Zhao, Tapio Kesti, Hasan Uğurlu, Andreas S Baur, Riku Fagerlund, Kalle Saksela
When studying how HIV-1 Nef can promote packaging of the proinflammatory transmembrane protease TACE into extracellular vesicles (EV) we have revealed a novel tyrosine kinase-regulated unconventional protein secretion (UPS) pathway for TACE. When TACE was expressed without its trafficking co-factor iRhom allosteric Hck activation by Nef triggered translocation of TACE into EVs. This process was insensitive to blocking of classical secretion by inhibiting ER to Golgi transport, and involved a distinct form of TACE devoid of normal glycosylation and incompletely processed for prodomain removal...
December 20, 2018: Traffic
Suriakarthiga Ganesan, Marjan Tavassoli, Maria L Sosa Ponce, Brittney Shabits, Mark Mahadeo, Elmar J Prenner, Mauricio R Terebiznik, Vanina Zaremberg
Diacylglycerol (DAG) is a key signaling lipid and intermediate in lipid metabolism. Our knowledge of DAG distribution and dynamics in cell membranes is limited. Using live-cell fluorescence microscopy we investigated the localization of yeast cytosolic-facing pools of DAG in response to conditions where lipid homeostasis and DAG levels were known to be altered. Two main pools were monitored over time using DAG sensors. One pool was associated with vacuolar membranes and the other localized to sites of polarized growth...
December 20, 2018: Traffic
Christina Funk, Verena Raschbichler, Diana Lieber, Jens Wetschky, Eileen Arnold, Jacqueline Leimser, Michael Biggel, Caroline C Friedel, Zsolt Ruzsics, Susanne M Bailer
Morphogenesis of herpesviral virions is initiated in the nucleus but completed in the cytoplasm. Mature virions contain more than 25 tegument proteins many of which perform both nuclear and cytoplasmic functions suggesting they shuttle between these compartments. While nuclear import of herpesviral proteins was shown to be crucial for viral propagation, active nuclear export and its functional impact are still poorly understood. To systematically analyse nuclear export of tegument proteins present in virions of Herpes simplex virus type 1 (HSV1) and Epstein Barr virus (EBV), the Nuclear EXport Trapped by RAPamycin assay (NEX-TRAP) was applied...
December 7, 2018: Traffic
Kossay Zaoui, Stephanie Duhamel, Christine Anna Parachoniak, Morag Park
Endocytic sorting of activated receptor tyrosine kinases (RTKs), alternating between recycling and degradative processes, controls signal duration, location, and surface complement of RTKs. The Microtubule (MT) plus-end tracking proteins (+TIPs) play essential roles in various cellular activities including translocation of intracellular cargo. However, mechanisms through which RTKs recycle back to the plasma membrane following internalisation in response to ligand remain poorly understood. We report that net outward-directed movement of endocytic vesicles containing the hepatocyte growth factor (HGF) Met RTK, requires recruitment of the +TIP, CLIP-170, as well as the association of CLIP-170 to MT plus-ends...
December 7, 2018: Traffic
Zara Y Weinberg, Manojkumar A Puthenveedu
The trafficking of G protein coupled-receptors (GPCRs) is one of the most exciting areas in cell biology due to recent advances demonstrating that GPCR signaling is spatially encoded. GPCRs, acting in a diverse array of physiological systems, can have differential signaling consequences depending on their subcellular localization. At the plasma membrane, GPCR organization could fine-tune the initial stages of receptor signaling by determining the magnitude of signaling and the type of effectors to which receptors can couple...
December 7, 2018: Traffic
Lauren M Del Bel, Julie A Brill
No abstract text is available yet for this article.
February 2019: Traffic
Yuna Kurokawa, Akane Yoshida, Emi Fujii, Kanna Tomioku, Hiroki Hayashi, Kenji Tanabe, Akikazu Fujita
Phosphatidylinositol 4-phophate (PtdIns(4)P) is an essential signaling molecule in the Golgi body, endosomal system, and plasma membrane and functions in the regulation of membrane trafficking, cytoskeletal organization, lipid metabolism and signal transduction pathways, all mediated by direct interaction with PtdIns(4)P-binding proteins. PtdIns(4)P was recently reported to have functional roles in autophagosome biogenesis. LC3 and GABARAP subfamilies and a small GTP-binding protein, Rab7, are localized on autophagosomal membranes and participate at each stage of autophagosome formation and maturation...
January 2019: Traffic
Karina Ringer, Jana Riehl, Manuel Müller, Jenny Dewes, Florian Hoff, Ralf Jacob
A highly specific transport and sorting machinery directing secretory cargo to the apical or basolateral plasma membrane maintains the characteristic polarized architecture of epithelial cells. This machinery comprises a defined set of transport carriers, which are crucial for cargo delivery to the correct membrane domain. Each carrier is composed of a distinct set of proteins to verify precise routing and cargo selection. Among these components, the dynamin-related GTPase Mx1 was identified on post-Golgi vesicles destined for the apical membrane of MDCK cells...
December 2018: Traffic
Spencer A Freeman, Sergio Grinstein
Macropinosomes, phagosomes and autolysosomes are comparatively large, quasi-spherical organelles that play essential functions in immunity and homeostasis. These vacuolar organelles are relatively short-lived, promptly fragmenting into smaller structures. Vacuolar resolution is mediated by tubulation and vesiculation, processes orchestrated by protein complexes that are recruited to highly curved membranes. Importantly, the surface-to-volume ratios of the tubules and vesicles generated during the resolution process are considerably larger than that of the parental vacuole...
December 2018: Traffic
Allison L Gilder, Hannah C Chapin, Valeria Padovano, Christina L Hueschen, Vanathy Rajendran, Michael J Caplan
Mutations in the genes encoding polycystin-1 (PC1) and polycystin 2 (PC2) cause autosomal dominant polycystic kidney disease. These transmembrane proteins colocalize in the primary cilia of renal epithelial cells, where they may participate in sensory processes. PC1 is also found in the apical membrane when expressed in cultured epithelial cells. PC1 undergoes autocatalytic cleavage, producing an extracellular N-terminal fragment that remains noncovalently attached to the transmembrane C-terminus. Exposing cells to alkaline solutions elutes the N-terminal fragment while the C-terminal fragment is retained in the cell membrane...
December 2018: Traffic
Fengjuan Wang, Raquel Gómez-Sintes, Patricia Boya
Lysosomes are membrane-enclosed organelles that mediate the intracellular degradation of macromolecules. They play an essential role in calcium regulation and have emerged as key signaling hubs in controlling the nutrient response. Maintaining lysosomal integrity and function is therefore crucial for cellular homeostasis. Different forms of stress can induce lysosomal membrane permeabilization (LMP), resulting in the translocation to the cytoplasm of intralysosomal components, such as cathepsins, inducing lysosomal-dependent cell death (LDCD)...
December 2018: Traffic
Heiko Lemcke, Robert David
microRNAs (miRNAs) are important epigenetic modulators of gene expression that control cellular physiology as well as tissue homeostasis, and development. In addition to the temporal aspects of miRNA-mediated gene regulation, the intracellular localization of miRNA is crucial for its silencing activity. Recent studies indicated that miRNA is even translocated between cells via gap junctional cell-cell contacts, allowing spatiotemporal modulation of gene expression within multicellular systems. Although non coding RNA remains a focus of intense research, studies regarding the intra-and intercellular mobility of small RNAs are still largely missing...
December 2018: Traffic
Beverley J Wilson, Jennifer L Allen, Patrick T Caswell
Cell migration is a vital process in development and disease, and while the mechanisms that control motility are relatively well understood on two-dimensional surfaces, the control of cell migration in three dimensions (3D) and in vivo has only recently begun to be understood. Vesicle trafficking pathways have emerged as a key regulatory element in migration and invasion, with the endocytosis and recycling of cell surface cargos, including growth factor and chemokine receptors, adhesion receptors and membrane-associated proteases, being of major importance...
December 2018: Traffic
Gildas Bourdais, Deirdre H McLachlan, Lydia M Rickett, Ji Zhou, Agnieszka Siwoszek, Heidrun Häweker, Matthew Hartley, Hannah Kuhn, Richard J Morris, Dan MacLean, Silke Robatzek
Expansion of gene families facilitates robustness and evolvability of biological processes but impedes functional genetic dissection of signalling pathways. To address this, quantitative analysis of single cell responses can help characterise the redundancy within gene families. We developed high-throughput quantitative imaging of stomatal closure, a response of plant guard cells, and performed a reverse genetic screen in a group of Arabidopsis mutants to five stimuli. Focussing on the intersection between guard cell signalling and the endomembrane system, we identified eight clusters based on the mutant stomatal responses...
November 16, 2018: Traffic
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