MGRN1 mediated ubiquitination of α‐tubulin regulates microtubule dynamics and intracellular transport
This study elucidates the effect of MGRN1 mediated ubiquitination of α‐tubulin in interphase cells. Here, we show that MGRN1 mediated ubiquitination regulates dynamics of EB1 labelled plus ends of microtubules. Intracellular transport of mitochondria and endosomes are affected in cultured cells where functional MGRN1 is depleted. Defects in microtubule‐dependent organellar transport are evident in cells where noncanonical K6 mediated ubiquitination of α‐tubulin by MGRN1 is compromised. Loss of MGRN1 has been previously correlated with late onset spongiform neurodegeneration. Mislocalised cytosolically exposed PrP (...
Source: Traffic - September 1, 2017 Category: Research Authors: Rukmini Mukherjee, Priyanka Majumder, Oishee Chakrabarti Tags: ORIGINAL ARTICLE Source Type: research

Nup42 and IP6 coordinate Gle1 stimulation of Dbp5/DDX19B for mRNA export in yeast and human cells
The mRNA lifecycle is driven through spatiotemporal changes in the protein composition of mRNA particles (mRNPs) that are triggered by RNA‐dependent DEAD‐box protein (Dbp) ATPases. As mRNPs exit the nuclear pore complex (NPC) in Saccharomyces cerevisiae, this remodeling occurs through activation of Dbp5 by inositol hexakisphosphate (IP6)‐bound Gle1. At the NPC, Gle1 also binds Nup42, but Nup42’s molecular function is unclear. Here we employ the power of structure‐function analysis in S. cerevisiae and human (h) cells, and find that the high‐affinity Nup42‐Gle1 interaction is integral to Dbp5 (hDDX19B) activat...
Source: Traffic - September 1, 2017 Category: Research Authors: Rebecca L. Adams, Aaron C. Mason, Laura Glass, Aditi, Susan R. Wente Tags: ORIGINAL ARTICLE Source Type: research

SNARE proteins in membrane trafficking
Abstract SNAREs (soluble N‐ethylmaleimide‐sensitive fusion protein attachment protein receptors) are the core machinery mediating membrane fusion. In this review, we provide an update on the recent progress on SNAREs regulating membrane fusion events, especially, the more detailed fusion processes dissected by well developed biophysical methods and in vitro single molecule analysis approaches. We also briefly summarize the relevant research from Chinese laboratories and highlight the significant contributions on our understanding of SNARE mediated membrane trafficking from scientists in China. Synopsis SNAREs are the ...
Source: Traffic - August 31, 2017 Category: Research Authors: Tuanlao Wang, Liangcheng Li, Wanjin Hong Tags: REVIEW Source Type: research

PIKfyve activity regulates reformation of terminal storage lysosomes from endolysosomes
ABSTRACT The protein complex composed of the kinase PIKfyve, the phosphatase FIG4 and the scaffolding protein VAC14 regulates the metabolism of phosphatidylinositol 3,5‐bisphosphate, which serves as both a signaling lipid and the major precursor for phosphatidylinositol 5‐phosphate. This complex is involved in the homeostasis of late endocytic compartments, but its precise role in maintaining the dynamic equilibrium of late endosomes, endolysosomes and lysosomes remains to be determined. Here, we report that inhibition of PIKfyve activity impairs terminal lysosome reformation from acidic and hydrolase‐active, but enl...
Source: Traffic - August 31, 2017 Category: Research Authors: Christin Bissig, Ilse Hurbain, Gra ça Raposo, Guillaume van Niel Tags: ORIGINAL ARTICLE Source Type: research

Yeast and other lower eukaryotic organisms for studies of Vps13 proteins in health and disease
Abstract Human Vps13 proteins are associated with several diseases, including the neurodegenerative disorder Chorea‐acanthocytosis (ChAc), yet the biology of these proteins is still poorly understood. Studies in Saccharomyces cerevisiae, Dictyostelium discoideum, Tetrahymena thermophila and Drosophila melanogaster point to the involvement of Vps13 in cytoskeleton organization, vesicular trafficking, autophagy, phagocytosis, endocytosis, proteostasis, sporulation and mitochondrial functioning. Recent findings show that yeast Vps13 binds to phosphatidylinositol lipids via four different regions and functions at membrane co...
Source: Traffic - August 28, 2017 Category: Research Authors: Weronika Rzepnikowska, Krzysztof Flis, Sandra Mu ñoz‐Braceras, Regina Menezes, Ricardo Escalante, Teresa Zoladek Tags: REVIEW Source Type: research

The role of S ‐acylation in protein trafficking
Protein S‐acylation, also known as palmitoylation, consists of the addition of a lipid molecule to one or more cysteine residues through a thioester bond. This modification, which is widespread in eukaryotes, is thought to affect over 12% of the human proteome. S‐acylation allows the reversible association of peripheral proteins with membranes or, in the case of integral membrane proteins, modulates their behavior within the plane of the membrane. This review focuses on the consequences of protein S‐acylation on intracellular trafficking and membrane association. We summarize relevant information that illustrates how...
Source: Traffic - August 25, 2017 Category: Research Authors: Jose L. Daniotti, Maria P. Pedro, Javier Valdez Taubas Tags: REVIEW Source Type: research

Transport of the alpha subunit of the voltage gated L ‐type calcium channel through the sarcoplasmic reticulum occurs prior to localization to triads and requires the beta subunit but not Stac3 in skeletal muscles
Contraction of skeletal muscle is initiated by excitation‐contraction (EC) coupling during which membrane voltage is transduced to intracellular Ca2+ release. EC coupling requires L‐type voltage gated Ca2+ channels (the dihydropyridine receptor or DHPR) located at triads, which are junctions between the transverse (T) tubule and sarcoplasmic reticulum (SR) membranes, that sense membrane depolarization in the T tubule membrane. Reduced EC coupling is associated with ageing, and disruptions of EC coupling result in congenital myopathies for which there are few therapies. The precise localization of DHPRs to triads is cri...
Source: Traffic - August 14, 2017 Category: Research Authors: Jeremy W. Linsley, I ‐Uen Hsu, Wenjia Wang, John Y. Kuwada Tags: ORIGINAL ARTICLE Source Type: research

Endoplasmic reticulum is the sorting core facility in the Golgi ‐lacking protozoan Giardia lamblia
Our understanding of protein and lipid trafficking in eukaryotic cells has been challenged by the finding of different forms of compartmentalization and cargo processing in protozoan parasites. Here, we show that, in the absence of a Golgi compartment in Giardia, proteins destined for secretion are directly sorted and packaged at specialized ER regions enriched in COPII coatomer complexes and ceramide. We also demonstrated that ER‐resident proteins are retained at the ER by the action of a KDEL receptor, which, in contrast to other eukaryotic KDEL receptors, showed no interorganellar dynamic but instead acts specifically...
Source: Traffic - August 14, 2017 Category: Research Authors: Nahuel Zamponi, Emiliano Zamponi, Gonzalo F. Mayol, Adriana Lanfredi ‐Rangel, Staffan G. Svärd, María C. Touz Tags: ORIGINAL ARTICLE Source Type: research

Issue Information
(Source: Traffic)
Source: Traffic - August 14, 2017 Category: Research Tags: ISSUE INFORMATION Source Type: research

Escherichia coli K1 utilises host macropinocytic pathways for invasion of brain microvascular endothelial cells
Abstract Eukaryotic cells utilise multiple endocytic pathways for specific uptake of ligands or molecules, and these pathways are commonly hijacked by pathogens to enable host cell invasion. Escherichia coli K1, a pathogenic bacterium that causes neonatal meningitis, invades the endothelium of the blood–brain barrier, but the entry route remains unclear. Here we demonstrate that the bacteria trigger an actin‐mediated uptake route, stimulating fluid phase uptake, membrane ruffling and macropinocytosis. The route of uptake requires intact lipid rafts as shown by cholesterol depletion. Using a variety of perturbants we ...
Source: Traffic - August 11, 2017 Category: Research Authors: Lip Nam Loh, Elizabeth M. C. McCarthy, Priyanka Narang, Naveed A. Khan, Theresa H. Ward Tags: ORIGINAL ARTICLE Source Type: research

Fusion and scission of membranes: ubiquitous topological transformations in cells
Abstract 2016 Nobel Prizes were awarded to Yoshinori Ohsumi for autophagy and to David Thouless, Duncan Haldane and Michael Kosterlitz for topological transitions. Both of these phenomena are intrinsically related when it comes to membranes. Here, we give a brief account on topological transformations of lipid membranes, commonly known as membrane fusion and membrane scission, and introduce the underlying topological invariant, the genus. The genus of a shape is a useful concept to distinguish unambiguously the processes of membrane fusion/scission and offers a simple method to describe complex, cellular membrane structure...
Source: Traffic - August 1, 2017 Category: Research Authors: Roland L. Knorr, Noboru Mizushima, Rumiana Dimova Tags: TRAFFIC INTERCHANGE Source Type: research

The Dense ‐Core Vesicle Maturation Protein CCCP‐1 Binds RAB‐2 and Membranes through its C‐terminal Domain
Abstract Dense‐core vesicles (DCVs) are secretory organelles that store and release modulatory neurotransmitters from neurons and endocrine cells. Recently, the conserved coiled‐coil protein CCCP‐1 was identified as a component of the DCV biogenesis pathway in the nematode C. elegans. CCCP‐1 binds the small GTPase RAB‐2 and colocalizes with it at the trans‐Golgi. Here we report a structure‐function analysis of CCCP‐1 to identify domains of the protein important for its localization, binding to RAB‐2, and function in DCV biogenesis. We find that the CCCP‐1 C‐terminal domain (CC3) has multiple activitie...
Source: Traffic - July 29, 2017 Category: Research Authors: J érôme Cattin‐Ortolá, Irini Topalidou, Annie Dosey, Alexey J. Merz, Michael Ailion Tags: ORIGINAL ARTICLE Source Type: research

Golgi α1,4‐Fucosyltransferase of Arabidopsis thaliana partially localizes at the nuclear envelope
Abstract We analyzed plant‐derived α1,4‐Fucosyltransferase (FucTc) homologs by reporter fusions and focused on representatives of the Brassicaceae and Solanaceae. Arabidopsis thaliana AtFucTc‐GFP or tomato LeFucTc‐GFP restored Lewis‐a formation in a fuctc mutant, confirming functionality in the trans‐Golgi. AtFucTc‐GFP partly accumulated at the nuclear envelope (NE) not observed for other homologs or truncated AtFucTc lacking the N‐terminus or catalytic domain. Analysis of At/LeFucTc‐GFP swap constructs with exchanged cytosolic, transmembrane and stalk (CTS), or only the CT regions, revealed that sorting...
Source: Traffic - July 28, 2017 Category: Research Authors: Stephan Rips, Manuel Frank, Annegret Elting, Jan Niklas Offenborn, Antje von Schaewen Tags: ORIGINAL ARTICLE Source Type: research

An automated quantitative image analysis tool for the identification of microtubule patterns in plants
High throughput confocal imaging poses challenges in the computational image analysis of complex subcellular structures such as the microtubule cytoskeleton. Here, we developed CellArchitect, an automated image analysis tool that quantifies changes to subcellular patterns illustrated by microtubule markers in plants. We screened microtubule‐targeted herbicides and demonstrate that high throughput confocal imaging with integrated image analysis by CellArchitect can distinguish effects induced by the known herbicides indaziflam and trifluralin. The same platform was used to examine six other compounds with herbicidal activ...
Source: Traffic - July 26, 2017 Category: Research Authors: Christine Faulkner, Ji Zhou, Alexandre Evrard, Gildas Bourdais, Dan MacLean, Heidrun H äweker, Peter Eckes, Silke Robatzek Tags: TOOLBOX Source Type: research

The Arl3 and Arl1 GTPases co ‐operate with Cog8 to regulate selective autophagy via Atg9 trafficking
In this study, we show that Arl3‐Arl1 small GTPase cascade co‐operates with the subunit of conserved oligomeric Golgi (COG) complex to control Cvt pathway but not non‐selective autophagy. The yeast strains with dysfunction of Arl3‐Arl1 cascade and COG complex accumulate Atg9 at the late Golgi in nutrient‐rich condition, thereby causing the defect of Cvt pathway. Thus, 2 Golgi‐endosomal traffic components co‐ordinately regulate the Cvt pathway by regulating Atg9 trafficking at the Golgi. (Source: Traffic)
Source: Traffic - July 25, 2017 Category: Research Authors: I ‐Hao Wang, Yi‐Jie Chen, Jia‐Wei Hsu, Fang‐Jen S. Lee Tags: ORIGINAL ARTICLE Source Type: research