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181.
Rylie B. Walsh Erica C. Dresselhaus Agata N. Becalska Matthew J. Zunitch Cassandra R. Blanchette Amy L. Scalera Tania Lemos So Min Lee Julia Apiki ShiYu Wang Berith Isaac Anna Yeh Kate Koles Avital A. Rodal 《The Journal of cell biology》2021,220(8)
Neuronal extracellular vesicles (EVs) play important roles in intercellular communication and pathogenic protein propagation in neurological disease. However, it remains unclear how cargoes are selectively packaged into neuronal EVs. Here, we show that loss of the endosomal retromer complex leads to accumulation of EV cargoes including amyloid precursor protein (APP), synaptotagmin-4 (Syt4), and neuroglian (Nrg) at Drosophila motor neuron presynaptic terminals, resulting in increased release of these cargoes in EVs. By systematically exploring known retromer-dependent trafficking mechanisms, we show that EV regulation is separable from several previously identified roles of neuronal retromer. Conversely, mutations in rab11 and rab4, regulators of endosome-plasma membrane recycling, cause reduced EV cargo levels, and rab11 suppresses cargo accumulation in retromer mutants. Thus, EV traffic reflects a balance between Rab4/Rab11 recycling and retromer-dependent removal from EV precursor compartments. Our data shed light on previous studies implicating Rab11 and retromer in competing pathways in Alzheimer’s disease, and suggest that misregulated EV traffic may be an underlying defect. 相似文献
182.
辽宁老铁山雀形目鸟类秋季迁徙初探 总被引:1,自引:0,他引:1
2000~2004年秋在辽宁旅顺老铁山自然保护区,通过鸟类环志和直接观察的方法,对该地区雀形目(Passeriformes)鸟类秋季迁徙规律进行了研究。5年共环志11 040只雀形目鸟类,发现8种保护区新记录种。结果表明,鸟类迁徙高峰大都集中在10月中下旬;气候条件与鸟类迁徙关系密切;不同年份优势种及种群数量均不同;鸟类的迁徙具有一定的顺序性和集群现象,但不同种类迁徙的种群大小又有差别;2004年雀形目鸟类的种类和数量都明显少于前4年,略有下降趋势。 相似文献
183.
The WD-repeat domain is a highly conserved recognition module in eukaryotes involved in diverse cellular processes. It is still not well understood how the bottom of a WD-repeat domain recognizes its binding partners. The WD-repeat-containing protein EED is one component of the PRC2 complex that possesses histone methyltransferase activity required for gene repression. Here we report the crystal structure of EED in complex with a 30 residue peptide from EZH2. The structure reveals that the peptide binds to the bottom of the WD-repeat domain of EED. The structural determinants of EZH2-EED interaction are present not only in EZH2 and EZH1 but also in its Drosophila homolog E(Z), suggesting that the recognition of ESC by E(Z) in Drosophila employs similar structural motifs. Structure-based mutagenesis identified critical residues from both EED and EZH2 for their interaction. The structure presented here may provide a template for understanding of how WD-repeat proteins recognize their interacting proteins. 相似文献
184.
A spectrophotometric assay to determine peptide transport has been developed. Using two chromogenic peptide mimetics, L-phenylalanyl-L-2-sulfanilylglycine (PSG) and L-phenylalanyl-L-3-thiaphenylalanine (PSP), the peptide transport patterns in individual cell species can be evaluated effectively. After the addition of PSG to a HeLa cell suspension, sulfanilic acid accumulated progressively inside, but not outside, the cells, demonstrating that PSG was transported wholly intact. The addition of PSP to the same cell suspension was followed immediately by extracellular thiophenol production. Measurement of the rate of thiophenol release thereby provided direct determination of PSP transport. The thiophenol release was consistent with Michaelis-Menten kinetics, with a K(m) of 0.016 mM and a V(max) of 5.07 nmol/min (1 x 10(6) cells/ml, pH 7.4, 37 degrees C). The resulting kinetic constants estimated were in agreement with values determined by single-substrate enzyme kinetics. Using PSP, transport kinetics of various dipeptides was examined by competitive spectrophotometry. As a result, dipeptides tested could be ranked in order of kinetic power for their transport. 相似文献
185.
Zhuo M 《Molecules and cells》2007,23(3):259-271
Investigation of molecular and cellular mechanisms of synaptic plasticity is the major focus of many neuroscientists. There are two major reasons for searching new genes and molecules contributing to central plasticity: first, it provides basic neural mechanism for learning and memory, a key function of the brain; second, it provides new targets for treating brain-related disease. Long-term potentiation (LTP), mostly intensely studies in the hippocampus and amygdala, is proposed to be a cellular model for learning and memory. Although it remains difficult to understand the roles of LTP in hippocampus-related memory, a role of LTP in fear, a simplified form of memory, has been established. Here, I will review recent cellular studies of LTP in the anterior cingulate cortex (ACC) and then compare studies in vivo and in vitro LTP by genetic/ pharmacological approaches. I propose that ACC LTP may serve as a cellular model for studying central sensitization that related to chronic pain, as well as pain-related cognitive emotional disorders. Understanding signaling pathways related to ACC LTP may help us to identify novel drug target for various mental disorders. 相似文献
186.
Woo Seung Son Kyu-Sung Jeong Sang Min Lim Ae Nim Pae 《Bioorganic & medicinal chemistry letters》2019,29(10):1168-1172
Highly effective and safe drugs for the treatment of neuropathic pain are urgently required and it was shown that blocking T-type calcium channels can be a promising strategy for drug development for neuropathic pain. We have developed pyrrolidine-based T-type calcium channel inhibitors by structural hybridization and subsequent assessment of in vitro activities against Cav3.1 and Cav3.2 channels. Profiling of in vitro ADME properties of compounds was also carried out. The representative compound 17h showed comparable in vivo efficacy to gabapentin in the SNL model, which indicates T-type calcium channel inhibitors can be developed as effective therapeutics for neuropathic pain. 相似文献
187.
188.
Liu Xiaoxiao Zhang Li Thu Pyone Myat Min Wenjian Yang Peng Li Ji Li Ping Xu Xiaojun 《中国科学:生命科学英文版》2021,64(8):1295-1310
Science China Life Sciences - Despite the use of many types of chemotherapies for pancreatic cancer, optimal efficacy has not been obtained so far. Pancreatic cancer shows a high incidence of TP53... 相似文献
189.
190.