Tau directs intracellular trafficking by regulating the forces exerted by kinesin and dynein teams
Organelles, proteins, and mRNA are transported bidirectionally along microtubules by plus‐end directed kinesin and minus‐end directed dynein motors. Microtubules are decorated by microtubule‐associated proteins (MAPs) that organize the cytoskeleton, regulate microtubule dynamics and modulate the interaction between motor proteins and microtubules to direct intracellular transport. Tau is a neuronal MAP that stabilizes axonal microtubules and crosslinks them into bundles. Dysregulation of tau leads to a range of neurodegenerative diseases known as tauopathies including Alzheimer's disease (AD). Tau reduces the process...
Source: Traffic - October 27, 2017 Category: Research Authors: Abdullah R. Chaudhary, Florian Berger, Christopher L. Berger, Adam G. Hendricks Tags: ORIGINAL ARTICLE Source Type: research
Phosphatidylinositol (4, 5) ‐bisphosphate targets double C2 domain protein B to the plasma membrane
Double C2 domain protein B (DOC2B) is a high‐affinity Ca2+ sensor that translocates from the cytosol to the plasma membrane (PM) and promotes vesicle priming and fusion. However, the molecular mechanism underlying its translocation and targeting to the PM in living cells is not completely understood. DOC2B interacts in vitro with the PM components phosphatidylserine, phosphatidylinositol (4, 5)‐bisphosphate [PI(4, 5)P2] and target SNAREs (t‐SNAREs). Here, we show that PI(4, 5)P2 hydrolysis at the PM of living cells abolishes DOC2B translocation, whereas manipulations of t‐SNAREs and other phosphoinositides have no ...
Source: Traffic - October 23, 2017 Category: Research Authors: Lirin Michaeli, Irit Gottfried, Maria Bykhovskaia, Uri Ashery Tags: ORIGINAL ARTICLE Source Type: research
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Source: Traffic - October 19, 2017 Category: Research Tags: ISSUE INFORMATION Source Type: research
V1b vasopressin receptor trafficking and signaling : role of arrestins, G proteins and Src kinase
The signaling pathway of G protein‐coupled receptors (GPCRs) is strongly linked to their trafficking profile. Little is known about the molecular mechanisms involved in the vasopressin receptor V1b subtype (V1bR) trafficking and its impact on receptor signaling and regulation. For this purpose, we investigated the role of β‐arrestins in receptor desensitization, internalization and recycling and attempted to dissect the V1bR‐mediated MAP Kinase pathway. Using β‐arrestin 1‐2 KO‐MEF cells, we demonstrated that both β‐arrestin 1 and 2 play a fundamental role in internalization and recycling of V1bR with a rap...
Source: Traffic - October 16, 2017 Category: Research Authors: Sanja Perkovska, Catherine M éjean, Mohammed Akli Ayoub, Juan Li, Floriane Hemery, Maithé Corbani, Nadine Laguette, Maria‐Angeles Ventura, Hélène Orcel, Thierry Durroux, Bernard Mouillac, Christiane Mendre Tags: ORIGINAL ARTICLE Source Type: research
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‐labeled 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 expo...
Source: Traffic - October 4, 2017 Category: Research Authors: Rukmini Mukherjee, Priyanka Majumder, Oishee Chakrabarti Tags: ORIGINAL ARTICLE Source Type: research
Recruitment of 7SL RNA to Assembling HIV ‐1 Virus‐Like Particles
Retroviruses incorporate specific host cell RNAs into virions. In particular, the host noncoding 7SL RNA is highly abundant in all examined retroviruses compared to its cellular levels or relative to common mRNAs such as actin. Using live cell imaging techniques, we have determined that the 7SL RNA does not arrive with the HIV‐1 RNA genome. Instead, it is recruited contemporaneous with assembly of the protein HIV‐1 Gag at the plasma membrane. Further, we demonstrate that complexes of 7SL RNA and Gag can be immunoprecipitated from both cytosolic and plasma membrane fractions. This indicates that 7SL RNAs likely interact...
Source: Traffic - October 1, 2017 Category: Research Authors: Michelle S. Itano, Helene Arnion, Sandra L. Wolin, Sanford M. Simon Tags: ORIGINAL ARTICLE Source Type: research
Structural insights into the nuclear import of the histone acetyltransferase MOF by importin α1
The histone acetyltransferase MOF (males‐absent‐on‐the‐first) acetylates the histone H4, a modification important for many biological processes, including chromatin organization, transcriptional regulation, DNA replication, recombination and repair, as well as autophagy. Depletion of MOF induces serious consequences due to the reduction of histone acetylation, such as nuclear morphological defects and cancer. Despite the critical roles of MOF in the nucleus, the structural or functional mechanisms of the nucleocytoplasmic transport of MOF remain elusive. Here, we identified novel importin α1‐specific nuclear loc...
Source: Traffic - October 1, 2017 Category: Research Authors: Weili Zheng, Rui Wang, Xi Liu, Siyu Tian, Benqiang Yao, Ang Chen, Shikai Jin, Yong Li Tags: ORIGINAL ARTICLE Source Type: research
Transcellular vesicular transport in epithelial and endothelial cells: Challenges and opportunities
Abstract
Vesicle‐mediated transcellular transport or simply “transcytosis” is a cellular process used to shuttle macromolecules such as lipoproteins, antibodies, and albumin from one surface of a polarized cell to the other. This mechanism is in contrast to the transit of small molecules such as anions, cations and amino acids that occur via uptake, diffusion through the cytosol and release and is also distinct from paracellular leak between cells. Importantly, transcytosis has evolved as a process to selectively move macromolecules between two neighboring yet unique microenvironments within a multicellular organism....
Source: Traffic - October 1, 2017 Category: Research Authors: Karen Y. Fung, Gregory D. Fairn, Warren L. Lee Tags: REVIEW Source Type: research
Membrane lipid order of sub ‐synaptic T cell vesicles correlates with their dynamics and function
Abstract
During an immune response, T cells survey antigen presenting cells for antigenic peptides via the formation of an interface known as an immunological synapse. Among the complex and dynamic biophysical phenomena occurring at this interface is the trafficking of sub‐synaptic vesicles carrying a variety of proximal signalling molecules. Here, we show that rather than being a homogeneous population, these vesicles display a diversity of membrane lipid order profiles, as measured using the environmentally sensitive dye di‐4‐ANEPPDHQ and multi‐spectral TIRF microscopy. Using live‐cell imaging, vesicle tracking...
Source: Traffic - October 1, 2017 Category: Research Authors: George W. Ashdown, David J. Williamson, Gary H.M. Soh, Nathan Day, Garth L. Burn, Dylan M. Owen Tags: ORIGINAL ARTICLE Source Type: research
Eps15R and clathrin regulate EphB2 ‐mediated cell repulsion
Abstract
Expression of Eph receptors and their ligands, the ephrins, have important functions in boundary formation and morphogenesis in both adult and embryonic tissue. The EphB receptors and ephrinB ligands are transmembrane proteins that are expressed in different cells and their interaction drives cell repulsion. For cell repulsion to occur, trans‐endocytosis of the inter‐cellular receptor‐ligand EphB‐ephrinB complex is required. The molecular mechanism underlying trans‐endocytosis is poorly defined. Here we show that the process is clathrin‐ and Eps15R‐mediated using Co115 colorectal cell lines stably ex...
Source: Traffic - October 1, 2017 Category: Research Authors: Emma Evergren, Neville Cobbe, Harvey T. McMahon Tags: ORIGINAL ARTICLE Source Type: research
Diatrack particle tracking software: review of applications and performance evaluation
Abstract
Object tracking is an instrumental tool supporting studies of cellular trafficking. There are three challenges in object tracking: the identification of targets; the precise determination of their position and boundaries, and the assembly of correct trajectories. This last challenge is particularly relevant when dealing with densely populated images with low signal‐to‐noise ratios ‐ conditions that are often encountered in applications such as organelle tracking, virus particle tracking, or single‐molecule imaging. We have developed a set of methods that can handle a wide variety of signal complexities. Th...
Source: Traffic - September 25, 2017 Category: Research Authors: Pascal Vallotton, Antoine M. van Oijen, Cynthia B. Whitchurch, Vladimir Gelfand, Leslie Yeo, Georgios Tsiavaliaris, Stephanie Heinrich, Elisa Dultz, Karsten Weis, David Gr ünwald Tags: TOOLBOX Source Type: research
CDK5 ‐dependent activation of dynein in the axon initial segment regulates polarized cargo transport in neurons
The unique polarization of neurons depends on selective sorting of axonal and somatodendritic cargos to their correct compartments. Axodendritic sorting and filtering occurs within the axon initial segment (AIS). However, the underlying molecular mechanisms responsible for this filter are not well understood. Here, we show that local activation of the neuronal‐specific kinase CDK5 is required to maintain AIS integrity, as depletion or inhibition of CDK5 induces disordered microtubule polarity and loss of AIS cytoskeletal structure. Furthermore, CDK5‐dependent phosphorylation of the dynein regulator Ndel1 is required fo...
Source: Traffic - September 23, 2017 Category: Research Authors: Eva Klinman, Mariko Tokito, Erika L.F. Holzbaur Tags: ORIGINAL ARTICLE Source Type: research
Phosphatidylinositol (4,5) ‐bisphosphate targets DOC2B to the plasma membrane
DOC2B is a high‐affinity Ca2+ sensor that translocates from the cytosol to the plasma membrane (PM) and promotes vesicle priming and fusion. However, the molecular mechanism underlying its translocation and targeting to the PM in living cells is not completely understood. DOC2B interacts in vitro with the PM components phosphatidylserine, phosphatidylinositol (4,5)‐bisphosphate [PI(4,5)P2] and target SNAREs (t‐SNAREs). Here we show that PI(4,5)P2 hydrolysis at the PM of living cells abolishes DOC2B translocation, whereas manipulations of t‐SNAREs and other phosphoinositides have no effect. Moreover, we were able to...
Source: Traffic - September 22, 2017 Category: Research Authors: Lirin Michaeli, Irit Gottfried, Maria Bykhovskaia, Uri Ashery Tags: ORIGINAL ARTICLE Source Type: research
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Source: Traffic - September 20, 2017 Category: Research Tags: ISSUE INFORMATION Source Type: research
Escherichia coli K1 utilizes host macropinocytic pathways for invasion of brain microvascular endothelial cells
Eukaryotic cells utilize 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 demonstrat...
Source: Traffic - September 20, 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
