Search results for "COFILIN"
showing 10 items of 11 documents
Cofilin and Neurodegeneration: New Functions for an Old but Gold Protein
2021
Cofilin is an actin-binding protein that plays a major role in the regulation of actin dynamics, an essential cellular process. This protein has emerged as a crucial molecule for functions of the nervous system including motility and guidance of the neuronal growth cone, dendritic spine organization, axonal branching, and synaptic signalling. Recently, other important functions in cell biology such as apoptosis or the control of mitochondrial function have been attributed to cofilin. Moreover, novel mechanisms of cofilin function regulation have also been described. The activity of cofilin is controlled by complex regulatory mechanisms, with phosphorylation being the most important, since t…
Methylmercury-induced developmental toxicity is associated with oxidative stress and cofilin phosphorylation. Cellular and human studies
2017
Environmental exposure to methylmercury (MeHg) during development is of concern because it is easily incorporated in children’s body both pre- and post-natal, it acts at several levels of neural pathways (mitochondria, cytoskeleton, neurotransmission) and it causes behavioral impairment in child. We evaluated the effects of prolonged exposure to 10–600 nM MeHg on primary cultures of mouse cortical (CCN) and of cerebellar granule cells (CGC) during their differentiation period. In addition, it was studied if prenatal MeHg exposure correlated with altered antioxidant defenses and cofilin phosphorylation in human placentas (n = 12) from the INMA cohort (Spain). Exposure to MeHg for 9 days in v…
The actin remodeling protein cofilin is crucial for thymic αβ but not γδ T-cell development
2018
Cofilin is an essential actin remodeling protein promoting depolymerization and severing of actin filaments. To address the relevance of cofilin for the development and function of T cells in vivo, we generated knock-in mice in which T-cell–specific nonfunctional (nf) cofilin was expressed instead of wild-type (WT) cofilin. Nf cofilin mice lacked peripheral αβ T cells and showed a severe thymus atrophy. This was caused by an early developmental arrest of thymocytes at the double negative (DN) stage. Importantly, even though DN thymocytes expressed the TCRβ chain intracellularly, they completely lacked TCRβ surface expression. In contrast, nf cofilin mice possessed normal numbers of γδ T cel…
The stressed cytoskeleton: How actin dynamics can shape stress-related consequences on synaptic plasticity and complex behavior
2015
Stress alters synaptic plasticity but the molecular and cellular mechanisms through which environmental stimuli modulate synaptic function remain to be elucidated. Actin filaments are the major structural component of synapses and their rearrangements by actin-binding proteins (ABPs) are critical for fine-tuning synaptic plasticity. Accumulating evidence suggests that some ABPs are specifically regulated by stress and stress-related effectors such as glucocorticoids and corticotropin releasing hormone. ABPs may thus be central in stress-induced perturbations at the level of synaptic plasticity, leading to impairments in behavioral domains including cognitive performance and social behavior.…
Cytotoxicity of tumor antigen specific human T cells is unimpaired by arginine depletion.
2013
Tumor-growth is often associated with the expansion of myeloid derived suppressor cells that lead to local or systemic arginine depletion via the enzyme arginase. It is generally assumed that this arginine deficiency induces a global shut-down of T cell activation with ensuing tumor immune escape. While the impact of arginine depletion on polyclonal T cell proliferation and cytokine secretion is well documented, its influence on chemotaxis, cytotoxicity and antigen specific activation of human T cells has not been demonstrated so far. We show here that chemotaxis and early calcium signaling of human T cells are unimpaired in the absence of arginine. We then analyzed CD8(+) T cell activation…
Neuronal polarization is impaired in mice lacking RhoE expression
2012
J. Neurochem. (2012) 121, 903–914. Abstract Proper development of neuronal networks relies on the polarization of the neurons, thus the establishment of two compartments, axons and dendrites, whose formation depends on cytoskeletal rearrangements. Rnd proteins are regulators of actin organization and they are important players in several aspects of brain development as neurite formation, axon guidance and neuron migration. We have recently demonstrated that mice lacking RhoE/Rnd3 expression die shortly after birth and have neuromotor impairment and neuromuscular alterations, indicating an abnormal development of the nervous system. In this study, we have further investigated the specific ro…
Cellular effects of bacterial N-3-Oxo-dodecanoyl-L-Homoserine lactone on the sponge Suberites domuncula (Olivi, 1792): insights into an intimate inte…
2014
International audience; Sponges and bacteria have lived together in complex consortia for 700 million years. As filter feeders, sponges prey on bacteria. Nevertheless, some bacteria are associated with sponges in symbiotic relationships. To enable this association, sponges and bacteria are likely to have developed molecular communication systems. These may include molecules such as N-acyl-L-homoserine lactones, produced by Gram-negative bacteria also within sponges. In this study, we examined the role of N-3-oxododecanoyl-L-homoserine lactone (3-oxo-C12-HSL) on the expression of immune and apoptotic genes of the host sponge Suberites domuncula. This molecule seemed to inhibit the sponge inn…
New protein clustering of breast cancer tissue proteomics using actin content as a cellularity indicator
2008
In the present study, we report the comparative proteome profiles of proteins solubilized from 37 breast cancer surgical tissues, normalized for the actin content. Blood-derived proteins were excluded from the analysis. Among the tumor-derived protein spots, a large proportion (39%) was found present in all patients. These included several glycolytic enzymes, detox and heat shock proteins, members of annexin and S100 protein families, cathepsin D, and two “rare” proteins, DDAH2 involved in the angiogenesis control, and the oncogene PARK7. Other proteins, such as psoriasin, galectin1, cofilin, peroredoxins, SH3L1, and others, showed sporadic presence and high expression level, which suggests…
p38α deficiency and oxidative stress cause cytokinesis failure in hepatocytes.
2015
Cytokinesis is the last step in mitosis and it implies re-organization of the actin cytoskeleton. Its failure is one of the major mechanisms of polyploidy and binucleation in mammals. Our aims were 1) to assess the role of redox-sensitive p38α MAPK in cytokinesis by studying the liver of wild type mice or liver-specific p38α knock-out mice; 2) to assess the role of oxidative stress associated with hepatocyte isolation on cytokinesis. When p38α was down-regulated in hepatocytes, MK2 phosphorylation on threonine 334 was completely abrogated. Activation of MNK-1, required for abscission of the intercellular bridge, was diminished. Key proteins of the RhoA pathway (phospho-PRK2, nuclear phospho…
Arginine deficiency leads to impaired cofilin dephosphorylation in activated human T lymphocytes
2012
The amino acid arginine is fundamentally involved in the regulation of the immune response during infection, inflammatory diseases and tumor growth. Arginine deficiency (e.g. due to the myeloid cell enzyme arginase) inhibits proliferation and effector functions of activated T lymphocytes. Here, we studied intracellular mechanisms mediating this suppression of human T lymphocytes. Our proteomic analysis revealed an impaired dephosphorylation of the actin-binding protein cofilin upon T-cell activation in the absence of arginine. We show that this correlates with alteration of actin polymerization and impaired accumulation of CD2 and CD3 in the evolving immunological synapse in T cell-antigen …