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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...
August 29, 2018: Traffic
Michael Sacher, Nassim Shahrzad, Hiba Kamel, Miroslav P Milev
The movement of proteins between cellular compartments requires the orchestrated actions of many factors including Rab family GTPases, soluble NSF attachment protein receptors (SNAREs) and so-called tethering factors. One such tethering factor is called TRAPP, and in humans, TRAPP proteins are distributed into two related complexes called TRAPP II and III. Although thought to act as a single unit within the complex, in the past few years it has become evident that some TRAPP proteins function independently of the complex...
August 27, 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 polycysin 2 (PC2) cause Autosomal Dominant Polycystic Kidney Disease (ADPKD). These transmembrane proteins co-localize 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 non-covalently 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...
August 20, 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)...
August 20, 2018: Traffic
Xiaolong Zhu, Juan Cai, Fan Zhou, Zulin Wu, Dan Li, Youbin Li, Zhiping Xie, Yiting Zhou, Yongheng Liang
Honokiol (HNK), an important medicinal component of Magnolia officinalis, is reported to possess pharmacological activities against a variety of diseases. However, the molecular mechanisms of HNK medicinal functions are not fully clear. To systematically study the mechanisms of HNK action, we screened a yeast mutant library based on the conserved nature of its genes among eukaryotes. We identified genes associated with increased resistance or sensitivity to HNK after mutation. After functional classification of these genes, we found that most HNK-resistant strains in the largest functional category were petites with mutations in mitochondrial genes, indicating that mitochondria were related to HNK resistance...
August 17, 2018: Traffic
Xu-Qiao Chen, Fang Fang, Jazmin B Florio, Edward Rockenstein, Eliezer Masliah, William C Mobley, Robert A Rissman, Chengbiao Wu
The cytosolic chaperonin T-complex protein (TCP) 1-ring complex (TRiC) has been shown to exert neuroprotective effects on axonal transport through clearance of mutant Huntingtin (mHTT) in Huntington's disease. However, it is presently unknown if TRiC also has any effect on axonal transport in wild type neurons. Here we examined how TRiC impacted the retrograde axonal transport of brain-derived neurotrophic factor (BDNF), which was significantly enhanced by TRiC subunit, leading to an increase in instantaneous velocity with a concomitant decrease in pauses for retrograde BDNF transport...
August 17, 2018: Traffic
Asako Goto, Mark Charman, Neale D Ridgway
Protein kinase D (PKD) controls secretion from the trans-Golgi network (TGN) by phosphorylating phosphatidylinositol 4-kinase IIIβ and proteins that bind and/or transfer phosphatidylinositol 4-phosphate (PtdIns-4P), such as oxysterol-binding protein (OSBP) and ceramide transfer protein. Here, we investigated the consequences of PKD phosphorylation of OSBP at endoplasmic reticulum (ER)-Golgi membrane contact sites (MCS). Results with OSBP phospho-mutants revealed that PKD phosphorylation did not affect sterol and PtdIns-4P binding, activation of sphingomyelin (SM) synthesis at Golgi-ER MCS or other OSBP phospho-sites...
August 12, 2018: Traffic
Cameron Schlegel, Lynne A Lapierre, Victoria G Weis, Janice A Williams, Izumi Kaji, Carolina Pinzon-Guzman, Nripesh Prasad, Braden Boone, Angela Jones, Hernan Correa, Shawn E Levy, Xianlin Han, Miao Wang, Kelly Thomsen, Sari Acra, James R Goldenring
Deficiency in diacylglycerol acyltransferase (DGAT1) is a rare cause of neonatal diarrhea, without a known mechanism or in vitro model. METHODS AND RESULTS: A patient presenting at our institution at 7 weeks of life with failure to thrive and diarrhea was found by whole-exome sequencing to have a homozygous DGAT1 truncation mutation. Duodenal biopsies showed loss of DGAT1 and deficits in apical membrane transporters and junctional proteins in enterocytes. When placed on a very low-fat diet, the patient's diarrhea resolved with normalization of brush border transporter localization in endoscopic biopsies...
August 10, 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...
July 30, 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...
July 27, 2018: Traffic
Meir Aridor
Our view of the secretory pathway has evolved from a morphological one to one that includes molecular mechanistic understanding of basic traffic components. These components include coat complexes involved in cargo sorting and budding and proteins that mediate targeting, tethering and fusion. The expanding repertoire of regulators that control basic traffic activities begins to paint a unified morphological-molecular view of secretion. The emerging picture provides key insights into the coupling of secretion with physiology...
July 6, 2018: Traffic
Divya Venkatesh, Ning Zhang, Martin Zoltner, Ricardo Canavate Del Pino, Mark C Field
The kinetoplastida and their close relatives are unicellular organisms prevalent within the biosphere and important for significant impacts on global health, economy and ecosystems. They are, under most models, an early branching lineage. Individual species adapted to highly diverse environments by adopting complex life styles; parasitic species can infect a wide range of eukaryotic hosts, while many relatives are free-living and some autotrophic from acquiring a plastid for photosynthesis. Adaptation is especially evident in the evolution of kinetoplastid cell surface architecture and is supported by endomembrane trafficking and serves as a platform for interaction with its environment...
July 4, 2018: Traffic
Katherine Bowers, Surjit K S Srai
Metal ion transporters of the Zrt- and Irt-like protein (ZIP, or SLC39A) family transport zinc, iron, manganese and/or cadmium across cellular membranes and into the cytosol. The 14 human ZIP family proteins are expressed in a wide variety of tissues and function in many different cellular processes. Many of these proteins (including ZIP1, 2, 3, 4, 5, 6/10, 8, 9, 11, 12, 14) are situated, at least some of the time, on the plasma membrane, where they mediate metal ion uptake into cells. Their level on the cell surface can be controlled rapidly via protein trafficking in response to the ions they transport...
June 28, 2018: Traffic
Jing Yang, Laurent Pieuchot, Gregory Jedd
The peroxisome matrix protein importomer has the remarkable ability to transport oligomeric protein substrates across the bilayer. However, the selectivity and relation between import and overall peroxisome homeostasis remain unclear. Here, we microinject artificial import substrates and employ quantitative microscopy to probe limits and capabilities of the importomer. DNA and polysaccharides are "piggyback" imported when noncovalently bound by a peroxisome targeting signal (PTS)-bearing protein. A dimerization domain that can be tuned to systematically vary the binding dissociation constant (Kd ) shows that a Kd in the millimolar range is sufficient to promote piggyback import...
October 2018: Traffic
Bogdan A Cichocki, Katrin Krumpe, Daniela G Vitali, Doron Rapaport
Tail-anchored (TA) proteins are embedded into their corresponding membrane via a single transmembrane segment at their C-terminus whereas the majority of the protein is facing the cytosol. So far, cellular factors that mediate the integration of such proteins into the mitochondrial outer membrane were not found. Using budding yeast as a model system, we identified the cytosolic Hsp70 chaperone Ssa1 and the peroxisome import factor Pex19 as import mediators for a subset of mitochondrial TA proteins. Accordingly, deletion of PEX19 results in: (1) growth defect under respiration conditions, (2) alteration in mitochondrial morphology, (3) reduced steady-state levels of the mitochondrial TA proteins Fis1 and Gem1, and (4) hampered in organello import of the TA proteins Fis1 and Gem1...
October 2018: Traffic
Guan Wang, Thierry Galli
A cell is able to sense the biomechanical properties of the environment such as the rigidity of the extracellular matrix and adapt its tension via regulation of plasma membrane and underlying actomyosin meshwork properties. The cell's ability to adapt to the changing biomechanical environment is important for cellular homeostasis and also cell dynamics such as cell growth and motility. Membrane trafficking has emerged as an important mechanism to regulate cell biomechanics. In this review, we summarize the current understanding of the role of cell mechanics in exocytosis, and reciprocally, the role of exocytosis in regulating cell mechanics...
October 2018: Traffic
Birol Cabukusta, Jacques Neefjes
Lysosomes are highly dynamic organelles that can move rapidly throughout the cell. They distribute in a rather immobile pool located around the microtubule-organizing center in a "cloud," and a highly dynamic pool in the cell periphery. Their spatiotemporal characteristics allow them to carry out multiple biological functions, such as cargo degradation, antigen presentation and plasma membrane repair. Therefore, it is not surprising that lysosomal dysfunction underlies various diseases, including cancer, neurodegenerative and autoimmune diseases...
October 2018: Traffic
Theodore L Steck, Yvonne Lange
The transverse asymmetry (sidedness) of phospholipids in plasma membrane bilayers is well characterized, distinctive, actively maintained and functionally important. In contrast, numerous studies using a variety of techniques have concluded that plasma membrane bilayer cholesterol is either mostly in the outer leaflet or the inner leaflet or is fairly evenly distributed. Sterols might simply partition according to their differing affinities for the asymmetrically disposed phospholipids, but some studies have proposed that it is actively transported to the outer leaflet...
October 2018: Traffic
Rebecca L Adams, Aaron C Mason, Laura Glass, Aditi, Susan R Wente
No abstract text is available yet for this article.
August 2018: Traffic
Luis-Carlos Tábara, Juan-Jesús Vicente, Joanna Biazik, Eeva-Liisa Eskelinen, Olivier Vincent, Ricardo Escalante
The multispanning membrane protein vacuole membrane protein 1 (VMP1) marks and regulates endoplasmic reticulum (ER)-domains associated with diverse ER-organelle membrane contact sites. A proportion of these domains associate with endosomes during their maturation and remodeling. We found that these VMP1 domains are enriched in choline/ethanolamine phosphotransferase and phosphatidylinositol synthase (PIS1), 2 ER enzymes required for the synthesis of various phospholipids. Interestingly, the lack of VMP1 impairs the formation of PIS1-enriched ER domains, suggesting a role in the distribution of phosphoinositides...
August 2018: Traffic
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