Spatial ‐Specific Functions in Retrograde Neuronal Signalling
Abstract Neurons are highly polarized cells, possessing long axons that can extend to more than 1‐meter long in adult humans. In order to survive and maintain proper functions, neurons have to respond accurately in both space and time to intra‐ or inter‐cellular cues. The regulation of these comprehensive responses involves ligand‐receptor interactions, trafficking and local protein synthesis. Alterations in these mechanisms can lead to cellular dysfunction and disease. Although studies on the transport and localization of signalling endosomes along the axon have shed light on some central pathways of neuronal surv...
Source: Traffic - April 1, 2017 Category: Research Authors: Eitan Erez Zahavi, Roy Maimon, Eran Perlson Tags: REVIEW Source Type: research

Recent progress in autophagic lysosome reformation
Abstract Autophagic lysosome reformation (ALR) is the terminal step of autophagy and is essential for maintaining lysosome homeostasis during autophagy. During ALR, tubules are extruded from autolysosomes, and small vesicles named proto‐lysosomes, which are composed of lysosomal membrane components, are generated from these tubules. Eventually, proto‐lysosomes mature into functional lysosomes. In this review, we will summarize recent progress in understanding the regulation, mechanisms and physiological functions of ALR. (Source: Traffic)
Source: Traffic - March 31, 2017 Category: Research Authors: Yang Chen, Li Yu Tags: REVIEW Source Type: research

Cell Biology in China: Focusing on the Lysosome
Abstract The view that lysosomes are merely the recycling bins of the cell has changed greatly during recent years. Lysosomes are now known to play a central role in signal transduction, cellular adaptation, plasma membrane repair, immune responses and many other fundamental cellular processes. In conjunction with the seminal discoveries made by international colleagues, many important questions regarding lysosomes are being addressed by Chinese scientists. In this review, we briefly summarize recent exciting findings in China on lysosomal signaling, biogenesis, integrity and physiological functions. (Source: Traffic)
Source: Traffic - March 30, 2017 Category: Research Authors: Chonglin Yang, Xiaochen Wang Tags: REVIEW Source Type: research

HAI ‐2 stabilizes, inhibits, and regulates SEA‐cleavage‐dependent secretory transport of matriptase
We describe three mutations in the binding loop of the HAI‐2 Kunitz domain 1 (K42N, C47F, and R48L) that cause a delay in the SEA domain cleavage of matriptase, leading to accumulation of non‐SEA domain cleaved matriptase in the ER. Two of the HAI‐2 Kunitz domain 1 mutants investigated, C47F and R48L, also displayed a reduced ability to proteolytically silence matriptase, suggesting that HAI‐2 inhibits the proteolytic activity of matriptase in the secretory pathway. (Source: Traffic)
Source: Traffic - March 28, 2017 Category: Research Authors: Annika W. Nonboe, Oliver Krigslund, Christoffer Soendergaard, Signe Skovbjerg, Stine Friis, Martin Nybo Andersen, Vincent Ellis, Makiko Kawaguchi, Hiroaki Kataoka, Thomas H. Bugge, Lotte K. Vogel Tags: ORIGINAL ARTICLE Source Type: research

Regulation of dynein ‐dynactin‐driven vesicular transport
Most of the long‐range intracellular movements of vesicles, organelles and other cargoes are driven by microtubule (MT)‐based molecular motors. Cytoplasmic dynein, a multisubunit protein complex, with the aid of dynactin, drives transport of a wide variety of cargoes towards the minus end of MTs. In this article, I review our current understanding of the mechanisms underlying spatiotemporal regulation of dynein‐dynactin‐driven vesicular transport with a special emphasis on the many steps of directional movement along MT tracks. These include the recruitment of dynein to MT plus ends, the activation and processivity...
Source: Traffic - March 28, 2017 Category: Research Authors: Jia ‐Jia Liu Tags: REVIEW Source Type: research

Issue Information
(Source: Traffic)
Source: Traffic - March 21, 2017 Category: Research Tags: ISSUE INFORMATION Source Type: research

HIV infection is influenced by dynamin at three independent points in the viral life cycle
Abstract CD4 T cells are important cellular targets for HIV‐1, yet the primary site of HIV fusion remains unresolved. Candidate fusion sites are either the plasma membrane or from within endosomes. One area of investigation compounding the controversy of this field, is the role of the protein dynamin in the HIV life cycle. To understand the role of dynamin in primary CD4 T cells we combined dynamin inhibition with a series of complementary assays based on single particle tracking, HIV fusion, detection of HIV DNA products and active viral transcription. We identify three levels of dynamin influence on the HIV life cycle....
Source: Traffic - February 28, 2017 Category: Research Authors: Anupriya Aggarwal, Tina L. Hitchen, Lars Ootes, Samantha McAllery, Andrew Wong, Khanh Nguyen, Adam McCluskey, Phillip J. Robinson, Stuart G. Turville Tags: ORIGINAL ARTICLE Source Type: research

Importin β1 targeting by Hepatitis C Virus NS3/4A Protein Restricts IRF3 and NF‐κB Signaling of IFNB1 Antiviral Response
In this study, newly identified host interactors of hepatitis C virus (HCV) proteins were assessed for a role in modulating innate immune response. The analysis revealed enrichment for components of the nuclear transport machinery and the crucial interaction with NS3/4A protein in suppression of interferon‐β (IFNB1) induction. Using a comprehensive microscopy‐based high‐content screening approach combined to the gene silencing of nuclear transport factors, we showed that NS3/4A‐interacting proteins control the nucleocytoplasmic trafficking of IFN regulatory factor 3 (IRF3) and NF‐κB p65 upon Sendai virus (SeV) ...
Source: Traffic - February 28, 2017 Category: Research Authors: Bridget Gagn é, Nicolas Tremblay, Alex Y Park, Martin Baril, Daniel Lamarre Tags: ORIGINAL ARTICLE Source Type: research

Deleting the DAG Kinase Dgk1 Augments Yeast Vacuole Fusion Through Increased Ypt7 Activity and Altered Membrane Fluidity
ABSTRACT Diacylglycerol (DAG) is a fusogenic lipid that can be produced through phospholipase C activity on phosphatidylinositol 4,5‐bisphosphate [PI(4,5)P2], or through phosphatidic acid (PA) phosphatase activity. The fusion of Saccharomyces cerevisiae vacuoles requires DAG, PA and PI(4,5)P2, and the production of these lipids is thought to provide temporally specific stoichiometries that are critical for each stage of fusion. Furthermore, DAG and PA can be interconverted by the DAG kinase Dgk1 and the PA phosphatase Pah1. Previously we found that pah1Δ vacuoles were fragmented, blocked in SNARE priming and showed arre...
Source: Traffic - February 28, 2017 Category: Research Authors: Gregory E. Miner, Matthew L. Starr, Logan R. Hurst, Rutilio A. Fratti Tags: ORIGINAL ARTICLE Source Type: research

The Axonal Transport Motor Kinesin ‐2 Navigates Microtubule Obstacles via Protofilament Switching
ABSTRACT Axonal transport involves kinesin motors trafficking cargo along microtubules that are rich in microtubule‐associated proteins (MAPs). Much attention has focused on the behavior of kinesin‐1 in the presence of MAPs, which has overshadowed understanding the contribution of other kinesins such as kinesin‐2 in axonal transport. We have previously shown that, unlike kinesin‐1, kinesin‐2 in vitro motility is insensitive to the neuronal MAP Tau. However, the mechanism by which kinesin‐2 efficiently navigates Tau on the microtubule surface is unknown. We hypothesized that mammalian kinesin‐2 side‐step...
Source: Traffic - February 28, 2017 Category: Research Authors: Gregory J. Hoeprich, Keith J. Mickolajczyk, Shane R. Nelson, William O. Hancock, Christopher L. Berger Tags: ORIGINAL ARTICLE Source Type: research

C9orf72: At the intersection of lysosome cell biology and neurodegenerative disease
Abstract The discovery that expansion of a hexanucleotide repeat within a non‐coding region of the C9orf72 gene causes amyotrophic lateral sclerosis and frontotemporal dementia raised questions about C9orf72 protein function and potential disease relevance. The major predicted structural feature of the C9orf72 protein is a DENN domain. As DENN domains are best characterized for regulation of specific Rab GTPases, it has been proposed that C9orf72 may also act through regulation of a GTPase target. Recent genetic and cell biological studies furthermore indicate that the C9orf72 protein functions at lysosomes as part of a ...
Source: Traffic - February 28, 2017 Category: Research Authors: Joseph Amick, Shawn M. Ferguson Tags: REVIEW Source Type: research

Protein transport in growing and steady ‐state cilia
Abstract Cilia and eukaryotic flagella are threadlike cell extensions with motile and sensory functions. Their assembly requires intraflagellar transport (IFT), a bidirectional motor‐driven transport of protein carriers along the axonemal microtubules. IFT moves ample amounts of structural proteins including tubulin into growing cilia likely explaining its critical role for assembly. IFT continues in non‐growing cilia contributing to a variety of processes ranging from axonemal maintenance and the export of non‐ciliary proteins to cell locomotion and ciliary signaling. Here, we discuss recent data on cues regulating ...
Source: Traffic - February 28, 2017 Category: Research Authors: Karl F. Lechtreck, Julie C. Van De Weghe, J. Aaron Harris, Peiwei Liu Tags: REVIEW Source Type: research

Regulation of dynein –dynactin‐driven vesicular transport
ABSTRACT Most of the long‐range intracellular movements of vesicles, organelles and other cargoes are driven by microtubule‐based molecular motors. Cytoplasmic dynein, a multisubunit protein complex, with the aid of dynactin, drives transport of a wide variety of cargoes towards the minus end of microtubules. In the present article, we review our current understanding of the mechanisms underlying spatiotemporal regulation of dynein–dynactin‐driven vesicular transport with a special emphasis on the many steps of directional movement along microtubule tracks. These include the recruitment of dynein to microtubule plu...
Source: Traffic - February 28, 2017 Category: Research Authors: Jia ‐Jia Liu Tags: REVIEW Source Type: research

Issue Information
(Source: Traffic)
Source: Traffic - February 22, 2017 Category: Research Tags: Issue Information Source Type: research

μ2‐Dependent Endocytosis of N‐cadherin Is Regulated by β‐Catenin to Facilitate Neurite Outgrowth
Abstract Circuit formation in the brain requires neurite outgrowth throughout development to establish synaptic contacts with target cells. Active endocytosis of several adhesion molecules facilitates the dynamic exchange of these molecules at the surface and promotes neurite outgrowth in developing neurons. The endocytosis of N‐cadherin, a calcium‐dependent adhesion molecule, has been implicated in the regulation of neurite outgrowth, but the mechanism remains unclear. Here, we identified that a fraction of N‐cadherin internalizes through clathrin‐mediated endocytosis (CME). Two tyrosine‐based motifs in the cyto...
Source: Traffic - January 31, 2017 Category: Research Authors: Yi ‐ting Chen, Chin‐Yin Tai Tags: ORIGINAL ARTICLE Source Type: research