99 research outputs found
The N-Myc Down Regulated Gene1 (NDRG1) Is a Rab4a Effector Involved in Vesicular Recycling of E-Cadherin
Cell to cell adhesion is mediated by adhesion molecules present on the cell surface. Downregulation of molecules that form the adhesion complex is a characteristic of metastatic cancer cells. Downregulation of the N-myc down regulated gene1 (NDRG1) increases prostate and breast metastasis. The exact function of NDRG1 is not known. Here by using live cell confocal microscopy and in vitro reconstitution, we report that NDRG1 is involved in recycling the adhesion molecule E-cadherin thereby stabilizing it. Evidence is provided that NDRG1 recruits on recycling endosomes in the Trans Golgi network by binding to phosphotidylinositol 4-phosphate and interacts with membrane bound Rab4aGTPase. NDRG1 specifically interacts with constitutively active Rab4aQ67L mutant protein and not with GDP-bound Rab4aS22N mutant proving NDRG1 as a novel Rab4a effector. Transferrin recycling experiments reveals NDRG1 colocalizes with transferrin during the recycling phase. NDRG1 alters the kinetics of transferrin recycling in cells. NDRG1 knockdown cells show a delay in recycling transferrin, conversely NDRG1 overexpressing cells reveal an increase in rate of transferrin recycling. This novel finding of NDRG1 as a recycling protein involved with recycling of E-cadherin will aid in understanding NDRG1 role as a metastasis suppressor protein
Influence of personality and fatalistic belief on taxi driver behaviour
The religious perception among individuals in sub-Saharan Africa that the ‘Big Five’ personality dimensions and fatalism are predictors of drivers’ behaviours and road accidents has received little scientific investigations. This paucity of research in the roles of psychological factors such as personality and fatalistic beliefs in shaping positive driver behaviour and attitudes has thus provided motivation for the conduct of this quantitative study. We collected data from 203 conveniently sampled taxi drivers in Gauteng province of South Africa by means of a structured questionnaire. Our analysis, using Structural Equation Modelling, found significant positive relationships between agreeableness and positive driver behaviour, conscientiousness and positive driver behaviour, fatalism and extraversion, as well as fatalism and positive driver behaviour. The results highlighted the dimensions of being methodical, organised, and risk aversive on the road, on the one hand, and being social, cooperative, and good-natured, on the other hand. Findings of the study further indicated that fatalistic beliefs are prevalent and indeed characteristic of individuals who are sociable, gregarious, and assertive. These individuals tend to uphold their religious and spiritual beliefs in the linkages between road accidents and destiny. Insights provided by this study could assist the Department of Transport and related Road Safety Authorities in designing road safety campaigns that addresses the erroneous beliefs by drivers that road accidents are pre-destined, and not as a result of individual’s driving behaviour.DHE
Myelin Proteomics: Molecular Anatomy of an Insulating Sheath
Fast-transmitting vertebrate axons are electrically insulated with multiple layers of nonconductive plasma membrane of glial cell origin, termed myelin. The myelin membrane is dominated by lipids, and its protein composition has historically been viewed to be of very low complexity. In this review, we discuss an updated reference compendium of 342 proteins associated with central nervous system myelin that represents a valuable resource for analyzing myelin biogenesis and white matter homeostasis. Cataloging the myelin proteome has been made possible by technical advances in the separation and mass spectrometric detection of proteins, also referred to as proteomics. This led to the identification of a large number of novel myelin-associated proteins, many of which represent low abundant components involved in catalytic activities, the cytoskeleton, vesicular trafficking, or cell adhesion. By mass spectrometry-based quantification, proteolipid protein and myelin basic protein constitute 17% and 8% of total myelin protein, respectively, suggesting that their abundance was previously overestimated. As the biochemical profile of myelin-associated proteins is highly reproducible, differential proteome analyses can be applied to material isolated from patients or animal models of myelin-related diseases such as multiple sclerosis and leukodystrophies
The Polarity Protein Scribble Regulates Myelination and Remyelination in the Central Nervous System
The development and regeneration of myelin by oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), requires profound changes in cell shape that lead to myelin sheath initiation and formation. Here, we demonstrate a requirement for the basal polarity complex protein Scribble in CNS myelination and remyelination. Scribble is expressed throughout oligodendroglial development and is up-regulated in mature oligodendrocytes where it is localised to both developing and mature CNS myelin sheaths. Knockdown of Scribble expression in cultured oligodendroglia results in disrupted morphology and myelination initiation. When Scribble expression is conditionally eliminated in the myelinating glia of transgenic mice, myelin initiation in CNS is disrupted, both during development and following focal demyelination, and longitudinal extension of the myelin sheath is disrupted. At later stages of myelination, Scribble acts to negatively regulate myelin thickness whilst suppressing the extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAP) kinase pathway, and localises to non-compact myelin flanking the node of Ranvier where it is required for paranodal axo-glial adhesion. These findings demonstrate an essential role for the evolutionarily-conserved regulators of intracellular polarity in myelination and remyelination
Systematic analysis of copy number variants of a large cohort of orofacial cleft patients identifies candidate genes for orofacial clefts
Validation of Coping Styles and Emotions Undergraduate Inventory on Romanian Psychology Students
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