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Lobov IB Rao S Carroll TJ Vallance JE Ito M Ondr JK Kurup S Glass DA Patel MS Shu W Morrisey EE McMahon AP Karsenty G Lang RA 《Nature》2005,437(7057):417-421
Macrophages have a critical role in inflammatory and immune responses through their ability to recognize and engulf apoptotic cells. Here we show that macrophages initiate a cell-death programme in target cells by activating the canonical WNT pathway. We show in mice that macrophage WNT7b is a short-range paracrine signal required for WNT-pathway responses and programmed cell death in the vascular endothelial cells of the temporary hyaloid vessels of the developing eye. These findings indicate that macrophages can use WNT ligands to influence cell-fate decisions--including cell death--in adjacent cells, and raise the possibility that they do so in many different cellular contexts. 相似文献
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Gout AM;ADPKD Gene Variant Consortium Ravine D Harris PC Rossetti S Peters D Breuning M Henske EP Koizumi A Inoue S Shimizu Y Thongnoppakhun W Yenchitsomanus PT Deltas C Sandford R Torra R Turco AE Jeffery S Fontes M Somlo S Furu LM Smulders YM Mercier B Ferec C Burtey S Pei Y Kalaydjieva L Bogdanova N McCluskey M Geon LJ Wouters CH Reiterova J Stekrová J San Millan JL Aguiari G Del Senno L 《Nature genetics》2007,39(4):427-428
3.
The hypothalamus is a neural structure critical for expression of motivated behaviours that ensure survival of the individual
and the species. It is a heterogeneous structure, generally recognised to have four distinct regions in the rostrocaudal axis
(preoptic, supraoptic, tuberal and mammillary). The tuberal hypothalamus in particular has been implicated in the neural control
of appetitive motivation, including feeding and drug seeking. Here we review the role of the tuberal hypothalamus in appetitive
motivation. First, we review evidence that different regions of the hypothalamus exert opposing control over feeding. We then
review evidence that a similar bi-directional regulation characterises hypothalamic contributions to drug seeking and reward
seeking. Lateral regions of the dorsal tuberal hypothalamus are important for promoting reinstatement of drug seeking, whereas
medial regions of the dorsal tuberal hypothalamus are important for inhibiting this drug seeking after extinction training.
Finally, we review evidence that these different roles for medial versus lateral dorsal tuberal hypothalamus in promoting
or preventing reinstatement of drug seeking are mediated, at least in part, by different populations of hypothalamic neurons
as well as the neural circuits in which they are located. 相似文献
4.
Functional corticotropin releasing factor receptors in the primate peripheral sympathetic nervous system 总被引:8,自引:0,他引:8
R Udelsman J P Harwood M A Millan G P Chrousos D S Goldstein R Zimlichman K J Catt G Aguilera 《Nature》1986,319(6049):147-150
Corticotropin releasing factor (CRF) is a key hormone in the integrated response to stress, acting both as the major regulator of pituitary adrenocorticotropic hormone (ACTH) release and as a neuropeptide in the brain. The actions of CRF are mediated by specific plasma membrane receptors in the anterior pituitary gland and in discrete brain areas including the cerebral cortex and several regions related to the limbic system. In addition to the pituitary and central actions of CRF, systemic administration of the peptide in the rat, dog, monkey and man causes hypotension and tachycardia because of a decrease in peripheral vascular resistance. These observations, in conjunction with the finding of immunoreactive and bioactive CRF in peripheral tissues, suggest that the peptide is locally released in tissues to act as a neurotransmitter or paracrine hormone. As CRF is present in the adrenal medulla and the peptide is known to modulate the central activity of the autonomic nervous system, we investigated the possibility that CRF is involved in the regulation of the peripheral autonomic nervous system. Such an action of CRF is supported by our demonstration of specific CRF receptors in the monkey adrenal medulla and sympathetic ganglia. In the adrenal medulla, these receptors are coupled to adenylate cyclase and can stimulate the secretion of catecholamines and Met-enkephalin. 相似文献
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Graupera M Guillermet-Guibert J Foukas LC Phng LK Cain RJ Salpekar A Pearce W Meek S Millan J Cutillas PR Smith AJ Ridley AJ Ruhrberg C Gerhardt H Vanhaesebroeck B 《Nature》2008,453(7195):662-666
Phosphoinositide 3-kinases (PI3Ks) signal downstream of multiple cell-surface receptor types. Class IA PI3K isoforms couple to tyrosine kinases and consist of a p110 catalytic subunit (p110alpha, p110beta or p110delta), constitutively bound to one of five distinct p85 regulatory subunits. PI3Ks have been implicated in angiogenesis, but little is known about potential selectivity among the PI3K isoforms and their mechanism of action in endothelial cells during angiogenesis in vivo. Here we show that only p110alpha activity is essential for vascular development. Ubiquitous or endothelial cell-specific inactivation of p110alpha led to embryonic lethality at mid-gestation because of severe defects in angiogenic sprouting and vascular remodelling. p110alpha exerts this critical endothelial cell-autonomous function by regulating endothelial cell migration through the small GTPase RhoA. p110alpha activity is particularly high in endothelial cells and preferentially induced by tyrosine kinase ligands (such as vascular endothelial growth factor (VEGF)-A). In contrast, p110beta in endothelial cells signals downstream of G-protein-coupled receptor (GPCR) ligands such as SDF-1alpha, whereas p110delta is expressed at low level and contributes only minimally to PI3K activity in endothelial cells. These results provide the first in vivo evidence for p110-isoform selectivity in endothelial PI3K signalling during angiogenesis. 相似文献
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A SxIP motif interaction at the microtubule plus end is important for processive retrograde axonal transport 总被引:1,自引:1,他引:0
Mridu Kapur Michael T. Maloney Wei Wang Xinyu Chen Ivan Millan Trevor Mooney Jie Yang Yanmin Yang 《Cellular and molecular life sciences : CMLS》2014,71(20):4043-4054
The retrograde transport of endosomes within axons proceeds with remarkable uniformity despite having to navigate a discontinuous microtubule network. The mechanisms through which this navigation is achieved remain elusive. In this report, we demonstrate that access of SxIP motif proteins, such as BPAG1n4, to the microtubule plus end is important for the maintenance of processive and sustained retrograde transport along the axon. Disruption of this interaction at the microtubule plus end significantly increases endosome stalling. Our study thus provides strong insight into the role of plus-end-binding proteins in the processive navigation of cargo within the axon. 相似文献
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