排序方式: 共有33条查询结果,搜索用时 15 毫秒
21.
Curnis F Gasparri AM Longhi R Colombo B D'Alessio S Pastorino F Ponzoni M Corti A 《Cellular and molecular life sciences : CMLS》2012,69(16):2791-2803
Chromogranin A (CgA), a secretory protein expressed by many neuroendocrine cells, neurons, cardiomyocytes, and keratinocytes, is the precursor of various peptides that regulate the carbohydrate/lipid metabolism and the cardiovascular system. We have found that CgA, locally administered to injured mice, can accelerate keratinocyte proliferation and wound healing. This biological activity was abolished by the Asp(45)Glu mutation. CgA and its N-terminal fragments, but not the corresponding Asp(45)Glu mutants, could selectively recognize the αvβ6-integrin on keratinocytes (a cell-adhesion receptor that is up-regulated during wound healing) and regulate keratinocyte adhesion, proliferation, and migration. No binding was observed to other integrins such as αvβ3, αvβ5, αvβ8, α5β1, α1β1, α3β1, α6β4, α6β7 and α9β1. Structure-activity studies showed that the entire CgA(39-63) region is crucial for αvβ6 recognition (K(i) = 7 nM). This region contains an RGD site (residues CgA(43-45)) followed by an amphipathic α-helix (residues CgA(47-63)), both crucial for binding affinity and selectivity. These results suggest that the interaction of the RGD/α-helix motif of CgA with αvβ6 regulates keratinocyte physiology in wound healing. 相似文献
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Vicinanza M D'Angelo G Di Campli A De Matteis MA 《Cellular and molecular life sciences : CMLS》2008,65(18):2833-2841
Membrane trafficking is crucial in the homeostasis of the highly compartmentalized eukaryotic cells. This compartmentalization
occurs both at the organelle level, with distinct organelles maintaining their identities while also intensely interchanging
components, and at a sub-organelle level, with adjacent subdomains of the same organelle containing different sets of lipids
and proteins.Acentral question in the field is thus how this compartmentalization is established and maintained despite the
intense exchange of components and even physical continuities within the same organelle. The phosphorylated derivatives of
phosphatidylinositol, known as the phosphoinositides, have emerged as key components in this context, both as regulators of
membrane trafficking and as finely tuned spatial and temporal landmarks for organelle and sub-organelle domains. The central
role of the phosphoinositides in cell homeostasis is highlighted by the severe consequences of the derangement of their metabolism
caused by genetic deficiencies of the enzymes involved, and from the systematic hijacking of phosphoinositide metabolism that
pathogens operate to promote their entry and/or survival in host cells. (Part of a Multi-author Review) 相似文献
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K Angelo EA Rancz D Pimentel C Hundahl J Hannibal A Fleischmann B Pichler TW Margrie 《Nature》2012,488(7411):375-378
One defining characteristic of the mammalian brain is its neuronal diversity. For a given region, substructure, layer or even cell type, variability in neuronal morphology and connectivity persists. Although it is well known that such cellular properties vary considerably according to neuronal type, the substantial biophysical diversity of neurons of the same morphological class is typically averaged out and ignored. Here we show that the amplitude of hyperpolarization-evoked sag of membrane potential recorded in olfactory bulb mitral cells is an emergent, homotypic property of local networks and sensory information processing. Simultaneous whole-cell recordings from pairs of cells show that the amount of hyperpolarization-evoked sag potential and current (Ih) is stereotypic for mitral cells belonging to the same glomerular circuit. This is corroborated by a mosaic, glomerulus-based pattern of expression of the HCN2 (hyperpolarization-activated cyclic nucleotide-gated channel 2) subunit of the Ih channel. Furthermore, inter-glomerular differences in both membrane potential sag and HCN2 protein are diminished when sensory input to glomeruli is genetically and globally altered so that only one type of odorant receptor is universally expressed. Population diversity in this intrinsic property therefore reflects differential expression between local mitral cell networks processing distinct odour-related information. 相似文献
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Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis 总被引:55,自引:0,他引:55
Pluchino S Quattrini A Brambilla E Gritti A Salani G Dina G Galli R Del Carro U Amadio S Bergami A Furlan R Comi G Vescovi AL Martino G 《Nature》2003,422(6933):688-694
Widespread demyelination and axonal loss are the pathological hallmarks of multiple sclerosis. The multifocal nature of this chronic inflammatory disease of the central nervous system complicates cellular therapy and puts emphasis on both the donor cell origin and the route of cell transplantation. We established syngenic adult neural stem cell cultures and injected them into an animal model of multiple sclerosis--experimental autoimmune encephalomyelitis (EAE) in the mouse--either intravenously or intracerebroventricularly. In both cases, significant numbers of donor cells entered into demyelinating areas of the central nervous system and differentiated into mature brain cells. Within these areas, oligodendrocyte progenitors markedly increased, with many of them being of donor origin and actively remyelinating axons. Furthermore, a significant reduction of astrogliosis and a marked decrease in the extent of demyelination and axonal loss were observed in transplanted animals. The functional impairment caused by EAE was almost abolished in transplanted mice, both clinically and neurophysiologically. Thus, adult neural precursor cells promote multifocal remyelination and functional recovery after intravenous or intrathecal injection in a chronic model of multiple sclerosis. 相似文献
27.
Germline mutations and sequence variants of the macrophage scavenger receptor 1 gene are associated with prostate cancer risk 总被引:16,自引:0,他引:16
Xu J Zheng SL Komiya A Mychaleckyj JC Isaacs SD Hu JJ Sterling D Lange EM Hawkins GA Turner A Ewing CM Faith DA Johnson JR Suzuki H Bujnovszky P Wiley KE DeMarzo AM Bova GS Chang B Hall MC McCullough DL Partin AW Kassabian VS Carpten JD Bailey-Wilson JE Trent JM Ohar J Bleecker ER Walsh PC Isaacs WB Meyers DA 《Nature genetics》2002,32(2):321-325
Deletions on human chromosome 8p22-23 in prostate cancer cells and linkage studies in families affected with hereditary prostate cancer (HPC) have implicated this region in the development of prostate cancer. The macrophage scavenger receptor 1 gene (MSR1, also known as SR-A) is located at 8p22 and functions in several processes proposed to be relevant to prostate carcinogenesis. Here we report the results of genetic analyses that indicate that mutations in MSR1 may be associated with risk of prostate cancer. Among families affected with HPC, we identified six rare missense mutations and one nonsense mutation in MSR1. A family-based linkage and association test indicated that these mutations co-segregate with prostate cancer (P = 0.0007). In addition, among men of European descent, MSR1 mutations were detected in 4.4% of individuals affected with non-HPC as compared with 0.8% of unaffected men (P = 0.009). Among African American men, these values were 12.5% and 1.8%, respectively (P = 0.01). These results show that MSR1 may be important in susceptibility to prostate cancer in men of both African American and European descent. 相似文献
28.
Krassimira Angelova Angelo Felline Moon Lee Manish Patel David Puett Francesca Fanelli 《Cellular and molecular life sciences : CMLS》2011,68(7):1227-1239
The luteinizing hormone receptor (LHR) is a G protein-coupled receptor (GPCR) particularly susceptible to spontaneous pathogenic
gain-of-function mutations. Protein structure network (PSN) analysis on wild-type LHR and two constitutively active mutants,
combined with in vitro mutational analysis, served to identify key amino acids that are part of the regulatory network responsible
for propagating communication between the extracellular and intracellular poles of the receptor. Highly conserved amino acids
in the rhodopsin family GPCRs participate in the protein structural stability as network hubs in both the inactive and active
states. Moreover, they behave as the most recurrent nodes in the communication paths between the extracellular and intracellular
sides in both functional states with emphasis on the active one. In this respect, non-conservative loss-of-function mutations
of these amino acids is expected to impair the most relevant way of communication between activating mutation sites or hormone-binding
domain and G protein recognition regions. 相似文献
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Over the last years it has become evident that the nuclear envelope (NE) is more than a passive membrane barrier that separates
the nucleus from the cytoplasm. The NE not only controls the trafficking of macromolecules between the nucleoplasm and the
cytosol, but also provides anchoring sites for chromosomes and cytoskeleton to the nuclear periphery. Targeting of chromatin
to the NE might actually be part of gene expression regulation in eukaryotes. Mutations in certain NE proteins are associated
with a diversity of human diseases, including muscular dystrophy, neuropathy, lipodistrophy, torsion dystonia and the premature
aging condition progeria. Despite the importance of the NE for cell division and differentiation, relatively little is known
about its biogenesis and its role in human diseases. It is our goal to provide a comprehensive view of the NE and to discuss
possible implications of NE-associated changes for gene expression, chromatin organization and signal transduction.
Received 8 August 2005; received after revision 13 October 2005; accepted 13 October 2005 相似文献