Global and local mechanisms sustain axonal proteostasis of transmembrane proteins
Abstract The control of neuronal protein homeostasis or proteostasis is tightly regulated both spatially and temporally, assuring accurate and integrated responses to external or intrinsic stimuli. Local or autonomous responses in dendritic and axonal compartments are crucial to sustain function during development, physiology and in response to damage or disease. Axons are responsible for generating and propagating electrical impulses in neurons, and the establishment and maintenance of their molecular composition are subject to extreme constraints exerted by length and size. Proteins that require the secretory pathway, su...
Source: Traffic - January 31, 2017 Category: Research Authors: V íctor Hugo Cornejo, Alejandro Luarte, Andrés Couve Tags: REVIEW Source Type: research

Routes and Mechanisms of Post ‐Endosomal Cholesterol Trafficking: a Story that Never Ends
Abstract Mammalian cells acquire most exogenous cholesterol through receptor‐mediated endocytosis of low‐density lipoproteins (LDLs). After internalization, LDL cholesteryl esters are hydrolyzed to release free cholesterol, which then translocates to late endosomes (LEs)/lysosomes (LYs) and incorporates into the membranes by coordinated actions of Niemann‐Pick type C (NPC) 1 and NPC2 proteins. However, how cholesterol exits LEs/LYs and moves to other organelles remain largely unclear. Growing evidence has suggested that nonvesicular transport is critically involved in the post‐endosomal cholesterol trafficking. Num...
Source: Traffic - January 31, 2017 Category: Research Authors: Jie Luo, Luyi Jiang, Hongyuan Yang, Bao ‐Liang Song Tags: REVIEW Source Type: research

ER ‐to‐Golgi Blockade of Nascent Desmosomal Cadherins in SERCA2‐inhibited Keratinocytes: Implications for Darier's Disease
Abstract Darier's disease (DD) is an autosomal dominantly inherited skin disorder caused by mutations in SERCA2, a Ca2+ pump that transports Ca2+ from the cytosol to the endoplasmic reticulum (ER). Loss of desmosomes and keratinocyte cohesion is a characteristic feature of DD. Desmosomal cadherins (DC) are Ca2+‐dependent transmembrane adhesion proteins of desmosomes, which are mislocalized in the lesional but not perilesional skin of DD. We show here that inhibition of SERCA2 by two distinct inhibitors results in accumulation of DC precursors in keratinocytes, indicating ER‐to‐Golgi transport of nascent DC is blocked...
Source: Traffic - January 31, 2017 Category: Research Authors: Ning Li, Moonhee Park, Shengxiang Xiao, Zhi Liu, Luis A. Diaz Tags: ORIGINAL ARTICLE Source Type: research

Green fluorescent protein ‐tagged apolipoprotein E: A useful marker for the study of hepatic lipoprotein egress
Apolipoprotein E (ApoE), a component of very‐low‐density and high‐density lipoproteins, participates in many aspects of lipid transport in the bloodstream. Underscoring its important functions, ApoE isoforms have been associated with metabolic and circulatory disease. ApoE is also incorporated into hepatitis C virus (HCV) particles, and promotes their production and infectivity. Live cell imaging analysis of ApoE behavior during secretion from producing cells thus has the potential to reveal important details regarding lipoprotein and HCV particle biogenesis and secretion from cells. However, this approach requires e...
Source: Traffic - January 30, 2017 Category: Research Authors: Constantin N. Takacs, Ursula Andreo, Rachel L. Belote, Joan Pulupa, Margaret A. Scull, Caroline E. Gleason, Charles M. Rice, Sanford M. Simon Tags: TOOLBOX Source Type: research

Amyloid precursor protein traffics from the Golgi directly to early endosomes in an Arl5b ‐ and AP4‐dependent pathway
The intracellular trafficking and proteolytic processing of the membrane‐bound amyloid precursor protein (APP) are coordinated events leading to the generation of pathogenic amyloid‐beta (Aβ) peptides. The membrane transport of newly synthesized APP from the Golgi to the endolysosomal system is not well defined, yet it is likely to be critical for regulating its processing by β‐secretase (BACE1) and γ‐secretase. Here, we show that the majority of newly synthesized APP is transported from the trans‐Golgi network (TGN) directly to early endosomes and then subsequently to the late endosomes/lysosomes with very li...
Source: Traffic - January 29, 2017 Category: Research Authors: Wei Hong Toh, Jing Zhi A. Tan, Khalisah L. Zulkefli, Fiona J. Houghton, Paul A. Gleeson Tags: ORIGINAL ARTICLE Source Type: research

Exogenous lysophospholipids with large head groups perturb clathrin ‐mediated endocytosis
In this study, we have investigated how clathrin‐dependent endocytosis is affected by exogenously added lysophospholipids (LPLs). Addition of LPLs with large head groups strongly inhibits transferrin (Tf) endocytosis in various cell lines, while LPLs with small head groups do not. Electron and total internal reflection fluorescence microscopy (EM and TIRF) reveal that treatment with lysophosphatidylinositol (LPI) with the fatty acyl group C18:0 leads to reduced numbers of invaginated clathrin‐coated pits (CCPs) at the plasma membrane, fewer endocytic events per membrane area and increased lifetime of CCPs. Also, endocy...
Source: Traffic - January 29, 2017 Category: Research Authors: Ieva Ailte, Anne Berit D. Lingelem, Audun S. Kvalvaag, Simona Kavaliauskiene, Andreas Brech, Gerbrand Koster, Paul G. Dommersnes, Jonas Bergan, Tore Skotland, Kirsten Sandvig Tags: ORIGINAL ARTICLE Source Type: research

Beyond attachment: roles of DC ‐SIGN in dengue virus infection
Abstract DC‐SIGN, a C‐type lectin expressed on the plasma membrane by human immature dendritic cells, is a receptor for numerous viruses including Ebola, SARS, and dengue. A controversial question has been whether DC‐SIGN functions as a complete receptor for both binding and internalization of dengue virus (DENV) or whether it is solely a cell surface attachment factor, requiring either hand‐off to another receptor or a co‐receptor for internalization. To examine this question, we used four cell types: human immature dendritic cells and NIH3T3 cells expressing either wild type DC‐SIGN or two internalization‐d...
Source: Traffic - January 27, 2017 Category: Research Authors: Ping Liu, Marc Ridilla, Pratik Patel, Laurie Betts, Emily Gallichotte, Lidea Shahidi, Nancy L. Thompson, Ken Jacobson Tags: ORIGINAL ARTICLE Source Type: research

Issue Information
(Source: Traffic)
Source: Traffic - January 23, 2017 Category: Research Tags: Issue Information Source Type: research

Mitochondrial protein import in trypanosomes: Expect the unexpected
Mitochondria have many different functions, the most important one of which is oxidative phosphorylation. They originated from an endosymbiotic event between a bacterium and an archaeal host cell. It was the evolution of a protein import system that marked the boundary between the endosymbiotic ancestor of the mitochondrion and a true organelle that is under the control of the nucleus. In present day mitochondria more than 95% of all proteins are imported from the cytosol in a proces mediated by hetero‐oligomeric protein complexes in the outer and inner mitochondrial membranes. In this review we compare mitochondrial pro...
Source: Traffic - January 16, 2017 Category: Research Authors: Anke Harsman, Andr é Schneider Tags: REVIEW Source Type: research

Fundamental mechanisms deliver the Nobel Prize to Ohsumi
(Source: Traffic)
Source: Traffic - January 16, 2017 Category: Research Authors: Sharon A. Tooze, Lisa A. Hannan, Michael S. Marks, Tom H. Stevens, Trina A. Schroer Tags: TRANSIT AUTHORITY Source Type: research

Editorial process file includedExogenous Lysophospholipids with Large Head Groups Perturb Clathrin ‐Mediated Endocytosis
In this study, we have investigated how clathrin‐dependent endocytosis is affected by exogenously added lysophospholipids (LPLs). Addition of LPLs with large head groups strongly inhibits transferrin (Tf) endocytosis in various cell lines, while LPLs with small head groups do not. Electron and total internal reflection fluorescence microscopy (EM and TIRF) reveal that treatment with lysophosphatidylinositol (LPI) with the fatty acyl group C18:0 leads to reduced numbers of invaginated clathrin‐coated pits (CCPs) at the plasma membrane, fewer endocytic events per membrane area and increased lifetime of CCPs. Also, endocy...
Source: Traffic - December 31, 2016 Category: Research Authors: Ieva Ailte, Anne Berit Dyve Lingelem, Audun Sverre Kvalvaag, Simona Kavaliauskiene, Andreas Brech, Gerbrand Koster, Paul Gunnar Dommersnes, Jonas Bergan, Tore Skotland, Kirsten Sandvig Tags: ORIGINAL ARTICLE Source Type: research

GFP ‐tagged Apolipoprotein E: a useful marker for the study of hepatic lipoprotein egress
Abstract Apolipoprotein E (ApoE), a component of very‐low‐density and high‐density lipoproteins, participates in many aspects of lipid transport in the bloodstream. Underscoring its important functions, ApoE isoforms have been associated with metabolic and circulatory disease. ApoE is also incorporated into hepatitis C virus (HCV) particles, and promotes their production and infectivity. Live cell imaging analysis of ApoE behavior during secretion from producing cells thus has the potential to reveal important details regarding lipoprotein and HCV particle biogenesis and secretion from cells. However, this approach r...
Source: Traffic - December 30, 2016 Category: Research Authors: Constantin N. Takacs, Ursula Andreo, Rachel L. Belote, Joan Pulupa, Margaret A. Scull, Caroline E. Gleason, Charles M. Rice, Sanford M. Simon Tags: TOOLBOX Source Type: research

Distinct complexes of yeast Snx4 family SNX ‐BARs mediate retrograde trafficking of Snc1 and Atg27
ABSTRACT The yeast SNX4 sub‐family of SNX‐BAR proteins, Snx4/Atg24, Snx41, and Atg20/Snx42, are required for endocytic recycling and selective autophagy. Here we show that Snx4 forms two functionally distinct heterodimers: Snx4–Atg20 and Snx4–Snx41. Each heterodimer coats an endosome‐derived tubule that mediates retrograde sorting of distinct cargo; the v‐SNARE, Snc1, is a cargo of the Snx4‐Atg20 pathway, and Snx4‐Snx41 mediates retrograde sorting of Atg27, an integral membrane protein implicated in selective autophagy. Live cell imaging of individual endosomes shows that Snx4 and the Vps5‐Vps17 retromer ...
Source: Traffic - December 27, 2016 Category: Research Authors: Mengxiao Ma, Christopher G. Burd, Richard J. Chi Tags: Original Article Source Type: research

DNA ‐based probes for flow cytometry analysis of endocytosis and recycling
ABSTRACT The internalization of proteins plays a key role in cell development, cell signaling and immunity. We have previously developed a specific hybridization internalization probe (SHIP) to quantitate the internalization of proteins and particles into cells. Herein, we extend the utility of SHIP to examine both the endocytosis and recycling of surface receptors using flow cytometry. SHIP was used to monitor endocytosis of membrane‐bound transferrin receptor and its soluble ligand transferrin. SHIP enabled measurements of the proportion of surface molecules internalized, the internalization kinetics and the proportion...
Source: Traffic - December 26, 2016 Category: Research Authors: Claire Dumont, Ewa Czuba, Moore Chen, Jose A. Villadangos, Angus P.R. Johnston, Justine D. Mintern Tags: TOOLBOX Source Type: research

So Long Tom!
(Source: Traffic)
Source: Traffic - December 22, 2016 Category: Research Authors: Lisa A. Hannan, Michael S. Marks, Trina A. Schroer, Sharon A. Tooze Tags: Editorial Source Type: research