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101.
Dong-Hyung Cho Tomohiro Nakamura Stuart A. Lipton 《Cellular and molecular life sciences : CMLS》2010,67(20):3435-3447
Mitochondria are highly dynamic organelles that continuously undergo two opposite processes, fission and fusion. Mitochondrial
dynamics influence not only mitochondrial morphology, but also mitochondrial biogenesis, mitochondrial distribution within
the cell, cell bioenergetics, and cell injury or death. Drp1 mediates mitochondrial fission, whereas Mfn1/2 and Opa1 control
mitochondrial fusion. Neurons require large amounts of energy to carry out their highly specialized functions. Thus, mitochondrial
dysfunction is a prominent feature in a variety of neurodegenerative diseases. Mutations of Mfn2 and Opa1 lead to neuropathies
such as Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. Moreover, both Aβ peptide and mutant huntingtin
protein induce mitochondrial fragmentation and neuronal cell death. In addition, mutants of Parkinson’s disease-related genes
also show abnormal mitochondrial morphology. This review highlights our current understanding of abnormal mitochondrial dynamics
relevant to neuronal synaptic loss and cell death in neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s
disease and Huntington’s disease. 相似文献
102.
In Ha Cho Min Jung Lee Dae Hwan Kim Bora Kim Jeomil Bae Kyu Yeong Choi Seon-Myung Kim Yun Hyun Huh Kun Ho Lee Chong-Hyun Kim Woo Keun Song 《Cellular and molecular life sciences : CMLS》2013,70(22):4369-4383
Actin plays a fundamental role in the regulation of spine morphology (both shrinkage and enlargement) upon synaptic activation. In particular, actin depolymerization is crucial for the spine shrinkage in NMDAR-mediated synaptic depression. Here, we define the role of SPIN90 phosphorylation/dephosphorylation in regulating actin depolymerization via modulation of cofilin activity. When neurons were treated with NMDA, SPIN90 was dephosphorylated by STEP61 (striatal-enriched protein tyrosine phosphatase) and translocated from the spines to the dendritic shafts. In addition, phosphorylated SPIN90 bound cofilin and then inhibited cofilin activity, suggesting that SPIN90 dephosphorylation is a prerequisite step for releasing cofilin so that cofilin can adequately sever actin filaments into monomeric form. We found that SPIN90 YE, a phosphomimetic mutant, remained in the spines after NMDAR activation where it bound cofilin, thereby effectively preventing actin depolymerization. This led to inhibition of the activity-dependent redistribution of cortactin and drebrin A, as well as of the morphological changes in the spines that underlie synaptic plasticity. These findings indicate that NMDA-induced SPIN90 dephosphorylation and translocation initiates cofilin-mediated actin dynamics and spine shrinkage within dendritic spines, thereby modulating synaptic activity. 相似文献
103.
Park S Park SH Baek JY Jy YJ Kim KS Roth J Cho JW Choe KM 《Cellular and molecular life sciences : CMLS》2011,68(20):3377-3384
Modification of nuclear and cytosolic proteins by O-linked N-acetylglucosamine (O-GlcNAcylation) is ubiquitous in cells. The in vivo function of the protein O-GlcNAcylation, however, is not well understood. Here, we manipulated the cellular O-GlcNAcylation level in Drosophila and found that it promotes developmental growth by enhancing insulin signaling. This increase in growth is due mainly to
cell growth and not to cell proliferation. Our data suggest that the increase in the insulin signaling activity is mediated,
at least in part, through O-GlcNAcylation of Akt. These results indicate that O-GlcNAcylation is one of the crucial mechanisms involved in control of insulin signaling during Drosophila development. 相似文献
104.
105.
Side chains of Lys/Arg near transmembrane domain (TMD) membrane-water interfaces can 'snorkel', placing their positive charge near negatively charged phospholipid head groups; however, snorkelling's functional effects are obscure. Integrin β TMDs have such conserved basic amino acids. Here we use NMR spectroscopy to show that integrin β(3)(Lys?716) helps determine β(3) TMD topography. The α(ΙΙb)β(3) TMD structure indicates that precise β(3) TMD crossing angles enable the assembly of outer and inner membrane 'clasps' that hold the αβ TMD together to limit transmembrane signalling. Mutation of β(3)(Lys?716) caused dissociation of α(ΙΙb)β(3) TMDs and integrin activation. To confirm that altered topography of β(3)(Lys?716) mutants activated α(ΙΙb)β(3), we used directed evolution of β(3)(K716A) to identify substitutions restoring default state. Introduction of Pro(711) at the midpoint of β(3) TMD (A711P) increased α(ΙΙb)β(3) TMD association and inactivated integrin α(ΙΙb)β(3)(A711P,K716A). β(3)(Pro?711) introduced a TMD kink of 30?±?1° precisely at the border of the outer and inner membrane clasps, thereby decoupling the tilt between these segments. Thus, widely occurring snorkelling residues in TMDs can help maintain TMD topography and membrane-embedding, thereby regulating transmembrane signalling. 相似文献
106.
A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease 总被引:157,自引:0,他引:157
Ogura Y Bonen DK Inohara N Nicolae DL Chen FF Ramos R Britton H Moran T Karaliuskas R Duerr RH Achkar JP Brant SR Bayless TM Kirschner BS Hanauer SB Nuñez G Cho JH 《Nature》2001,411(6837):603-606
Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract, which is thought to result from the effect of environmental factors in a genetically predisposed host. A gene location in the pericentromeric region of chromosome 16, IBD1, that contributes to susceptibility to Crohn's disease has been established through multiple linkage studies, but the specific gene(s) has not been identified. NOD2, a gene that encodes a protein with homology to plant disease resistance gene products is located in the peak region of linkage on chromosome 16 (ref. 7). Here we show, by using the transmission disequilibium test and case-control analysis, that a frameshift mutation caused by a cytosine insertion, 3020insC, which is expected to encode a truncated NOD2 protein, is associated with Crohn's disease. Wild-type NOD2 activates nuclear factor NF-kappaB, making it responsive to bacterial lipopolysaccharides; however, this induction was deficient in mutant NOD2. These results implicate NOD2 in susceptibility to Crohn's disease, and suggest a link between an innate immune response to bacterial components and development of disease. 相似文献
107.
A new human HLA class II-related locus, DM 总被引:9,自引:0,他引:9
HLA class II molecules have a crucial role in the immune response to antigens. We have isolated two new class II-like complementary DNA sequences, RING6 and RING7, which map between the HLA-DNA and -DOB loci. They are novel members of the immunoglobulin gene family which may have diverged before the duplications that gave rise to the main class II loci. The RING6 and RING7 genes seem to encode alpha- and beta-chains of a previously undiscovered class II-related protein. 相似文献
108.
This paper presents an integration methodology for ma chining and measuring processes using OMM (On-Machine Measurement) technology b ased on CAD/CAM/CAI integration concept. OMM uses a CNC machining center as a me asuring station by changing the tools into measuring probes such as touch-type, laser and vision. Although the measurement accuracy is not good compared to tha t of the CMM (Coordinate Measuring Machine), there are distinctive advantages us ing OMM in real situation. In this paper, two topics a... 相似文献
109.
The effect of nicotine on ethanol-induced gastric ulcers in rats 总被引:1,自引:0,他引:1
Nicotine, in concentrations of 5 and 25 micrograms/ml drinking water, given ad libitum for 10 days, dose-dependently increased lesion formation and worsened ethanol-induced ulceration in rat stomachs. Daily fluid intake and b.wt gain were not adversely affected by nicotine pretreatment. 相似文献
110.
CHO Kyuhaeng LIN YanJun David G. EVANS LI DianQing 《科学通报(英文版)》2007,52(7):877-882
Nanoscale NiAl-NO3-LDHs with good crystallinity have been synthesized by a method, Separate Nucleation and Aging Steps (SNAS). An NiAl-NO3-LDHs/LDPE composite was prepared by blending NiAl-NO3-LDHs and LDPE in a heated double-roller mixer. The color of this composite changed from olive green to steel gray under UV irradiation. After heating at 80oC for 2 h, the color returned to olive green. The effect of varying the amount of added NiAl-NO3-LDHs and UV exposure time on the photochromic properties of the composite has been investigated. The results showed that the photochromic phenomenon becomes more apparent with increasing amount of NiAl-NO3-LDHs. When the amount reaches 5%, the composite exhibits good photochromic properties and reproducibility. The color change rate of the composite reaches a maximum when the irradiation time exceeds 20 min. The addition of LDPE improves the photochromic cyclability of NiAl-NO3-LDHs significantly. The addition of nanoscale NiAl-NO3-LDHs also improves the mechanical properties of LDPE to some extent. 相似文献