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31.
An increase in the concentration of cytosolic free Ca2+ is a key component regulating different cellular processes ranging from egg fertilization, active secretion and movement,
to cell differentiation and death. The multitude of phenomena modulated by Ca2+, however, do not simply rely on increases/decreases in its concentration, but also on specific timing, shape and sub-cellular
localization of its signals that, combined together, provide a huge versatility in Ca2+ signaling. Intracellular organelles and their Ca2+ handling machineries exert key roles in this complex and precise mechanism, and this review will try to depict a map of Ca2+ routes inside cells, highlighting the uniqueness of the different Ca2+ toolkit components and the complexity of the interactions between them. 相似文献
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An inflection point in genetics has been reached and was witnessed at the Genomics of Common Diseases meeting (http://www.nature.com/ng/meetings/genomics) co-sponsored by the Wellcome Trust, held at the Wellcome Trust Hinxton Conference Centre July 7-10, 2007 and co-organized by Tim Aitman, David Altshuler and Eddy Rubin. 相似文献
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FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity 总被引:13,自引:0,他引:13
Fanciulli M Norsworthy PJ Petretto E Dong R Harper L Kamesh L Heward JM Gough SC de Smith A Blakemore AI Froguel P Owen CJ Pearce SH Teixeira L Guillevin L Graham DS Pusey CD Cook HT Vyse TJ Aitman TJ 《Nature genetics》2007,39(6):721-723
Naturally occurring variation in gene copy number is increasingly recognized as a heritable source of susceptibility to genetically complex diseases. Here we report strong association between FCGR3B copy number and risk of systemic lupus erythematosus (P = 2.7 x 10(-8)), microscopic polyangiitis (P = 2.9 x 10(-4)) and Wegener's granulomatosis in two independent cohorts from the UK (P = 3 x 10(-3)) and France (P = 1.1 x 10(-4)). We did not observe this association in the organ-specific Graves' disease or Addison's disease. Our findings suggest that low FCGR3B copy number, and in particular complete FCGR3B deficiency, has a key role in the development of systemic autoimmunity. 相似文献
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A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter 总被引:2,自引:0,他引:2
Mitochondrial Ca(2+) homeostasis has a key role in the regulation of aerobic metabolism and cell survival, but the molecular identity of the Ca(2+) channel, the mitochondrial calcium uniporter, is still unknown. Here we have identified in silico a protein (named MCU) that shares tissue distribution with MICU1 (also known as CBARA1), a recently characterized uniporter regulator, is present in organisms in which mitochondrial Ca(2+) uptake was demonstrated and whose sequence includes two transmembrane domains. Short interfering RNA (siRNA) silencing of MCU in HeLa cells markedly reduced mitochondrial Ca(2+) uptake. MCU overexpression doubled the matrix Ca(2+) concentration increase evoked by inositol 1,4,5-trisphosphate-generating agonists, thus significantly buffering the cytosolic elevation. The purified MCU protein showed channel activity in planar lipid bilayers, with electrophysiological properties and inhibitor sensitivity of the uniporter. A mutant MCU, in which two negatively charged residues of the putative pore-forming region were replaced, had no channel activity and reduced agonist-dependent matrix Ca(2+) concentration transients when overexpressed in HeLa cells. Overall, these data demonstrate that the 40-kDa protein identified is the channel responsible for ruthenium-red-sensitive mitochondrial Ca(2+) uptake, thus providing a molecular basis for this process of utmost physiological and pathological relevance. 相似文献
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Lucia Banci Ivano Bertini Francesca Cantini Simone Ciofi-Baffoni 《Cellular and molecular life sciences : CMLS》2010,67(15):2563-2589
Copper is an essential but potentially harmful trace element required in many enzymatic processes involving redox chemistry.
Cellular copper homeostasis in mammals is predominantly maintained by regulating copper transport through the copper import
CTR proteins and the copper exporters ATP7A and ATP7B. Once copper is imported into the cell, several pathways involving a
number of copper proteins are responsible for trafficking it specifically where it is required for cellular life, thus avoiding
the release of harmful free copper ions. In this study we review recent progress made in understanding the molecular mechanisms
of copper transport in cells by analyzing structural features of copper proteins, their mode of interaction, and their thermodynamic
and kinetic parameters, thus contributing to systems biology of copper within the cell. 相似文献
38.
The seed habit represents a remarkable evolutionary advance in plant sexual reproduction. Since the Paleozoic, seeds carry a seed coat that protects, nourishes and facilitates the dispersal of the fertilization product(s). The seed coat architecture evolved to adapt to different environments and reproductive strategies in part by modifying its thickness. Here, we review the great natural diversity observed in seed coat thickness among angiosperms and its molecular regulation in Arabidopsis. 相似文献
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Resumen Los gránulos citoplasmáticos de células endoteliales de aorta de sapo fueron separados en fracciones subcelulares, obtenidas por centrifugación diferencial, de homogenados de esa arteria. Los sedimentos que contienen los gránulos, liberaron factores hipertensores bajo el efecto de un «shock» osmótico. 相似文献
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Claudia Compagnucci Monica Nizzardo Stefania Corti Ginevra Zanni Enrico Bertini 《Cellular and molecular life sciences : CMLS》2014,71(9):1623-1639
Neurogenesis is the developmental process regulating cell proliferation of neural stem cells, determining their differentiation into glial and neuronal cells, and orchestrating their organization into finely regulated functional networks. Can this complex process be recapitulated in vitro using induced pluripotent stem cell (iPSC) technology? Can neurodevelopmental and neurodegenerative diseases be modeled using iPSCs? What is the potential of iPSC technology in neurobiology? What are the recent advances in the field of neurological diseases? Since the applications of iPSCs in neurobiology are based on the capacity to regulate in vitro differentiation of human iPSCs into different neuronal subtypes and glial cells, and the possibility of obtaining iPSC-derived neurons and glial cells is based on and hindered by our poor understanding of human embryonic development, we reviewed current knowledge on in vitro neural differentiation from a developmental and cellular biology perspective. We highlight the importance to further advance our understanding on the mechanisms controlling in vivo neurogenesis in order to efficiently guide neurogenesis in vitro for cell modeling and therapeutical applications of iPSCs technology. 相似文献