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121.
Sato K Watanabe T Wang S Kakeno M Matsuzawa K Matsui T Yokoi K Murase K Sugiyama I Ozawa M Kaibuchi K 《Molecular biology of the cell》2011,22(17):3103-3119
Cadherin trafficking controls tissue morphogenesis and cell polarity. The endocytic adaptor Numb participates in apicobasal polarity by acting on intercellular adhesions in epithelial cells. However, it remains largely unknown how Numb controls cadherin-based adhesion. Here, we found that Numb directly interacted with p120 catenin (p120), which is known to interact with E-cadherin and prevent its internalization. Numb accumulated at intercellular adhesion sites and the apical membrane in epithelial cells. Depletion of Numb impaired E-cadherin internalization, whereas depletion of p120 accelerated internalization. Expression of the Numb-binding fragment of p120 inhibited E-cadherin internalization in a dominant-negative fashion, indicating that Numb interacts with the E-cadherin/p120 complex and promotes E-cadherin endocytosis. Impairment of Numb induced mislocalization of E-cadherin from the lateral membrane to the apical membrane. Atypical protein kinase C (aPKC), a member of the PAR complex, phosphorylated Numb and inhibited its association with p120 and α-adaptin. Depletion or inhibition of aPKC accelerated E-cadherin internalization. Wild-type Numb restored E-cadherin internalization in the Numb-depleted cells, whereas a phosphomimetic mutant or a mutant with defective α-adaptin-binding ability did not restore the internalization. Thus, we propose that aPKC phosphorylates Numb to prevent its binding to p120 and α-adaptin, thereby attenuating E-cadherin endocytosis to maintain apicobasal polarity. 相似文献
122.
Background
Members of the evolutionary conserved Ser/Thr kinase Unc-51 family are key regulatory proteins that control neural development in both vertebrates and invertebrates. Previous studies have suggested diverse functions for the Unc-51 protein, including axonal elongation, growth cone guidance, and synaptic vesicle transport.Methodology/Principal Findings
In this work, we have investigated the functional significance of Unc-51-mediated vesicle transport in the development of complex brain structures in Drosophila. We show that Unc-51 preferentially accumulates in newly elongating axons of the mushroom body, a center of olfactory learning in flies. Mutations in unc-51 cause disintegration of the core of the developing mushroom body, with mislocalization of Fasciclin II (Fas II), an IgG-family cell adhesion molecule important for axonal guidance and fasciculation. In unc-51 mutants, Fas II accumulates in the cell bodies, calyx, and the proximal peduncle. Furthermore, we show that mutations in unc-51 cause aberrant overshooting of dendrites in the mushroom body and the antennal lobe. Loss of unc-51 function leads to marked accumulation of Rab5 and Golgi components, whereas the localization of dendrite-specific proteins, such as Down syndrome cell adhesion molecule (DSCAM) and No distributive disjunction (Nod), remains unaltered. Genetic analyses of kinesin light chain (Klc) and unc-51 double heterozygotes suggest the importance of kinesin-mediated membrane transport for axonal and dendritic development. Moreover, our data demonstrate that loss of Klc activity causes similar axonal and dendritic defects in mushroom body neurons, recapitulating the salient feature of the developmental abnormalities caused by unc-51 mutations.Conclusions/Significance
Unc-51 plays pivotal roles in the axonal and dendritic development of the Drosophila brain. Unc-51-mediated membrane vesicle transport is important in targeted localization of guidance molecules and organelles that regulate elongation and compartmentalization of developing neurons. 相似文献123.
Daniel C. Teasley Shankar Parajuli Mai Nguyen Hayley R. Moore Elise Alspach Ying Jie Lock Yuchi Honaker Abhishek Saharia Helen Piwnica-Worms Sheila A. Stewart 《The Journal of biological chemistry》2015,290(24):15133-15145
The existence of redundant replication and repair systems that ensure genome stability underscores the importance of faithful DNA replication. Nowhere is this complexity more evident than in challenging DNA templates, including highly repetitive or transcribed sequences. Here, we demonstrate that flap endonuclease 1 (FEN1), a canonical lagging strand DNA replication protein, is required for normal, complete leading strand replication at telomeres. We find that the loss of FEN1 nuclease activity, but not DNA repair activities, results in leading strand-specific telomere fragility. Furthermore, we show that FEN1 depletion-induced telomere fragility is increased by RNA polymerase II inhibition and is rescued by ectopic RNase H1 expression. These data suggest that FEN1 limits leading strand-specific telomere fragility by processing RNA:DNA hybrid/flap intermediates that arise from co-directional collisions occurring between the replisome and RNA polymerase. Our data reveal the first molecular mechanism for leading strand-specific telomere fragility and the first known role for FEN1 in leading strand DNA replication. Because FEN1 mutations have been identified in human cancers, our findings raise the possibility that unresolved RNA:DNA hybrid structures contribute to the genomic instability associated with cancer. 相似文献
124.
Giang Ngan Khong Pratap Kumar Pati Frédérique Richaud Boris Parizot Przemyslaw Bidzinski Chung Duc Mai Martine Bès Isabelle Bourrié Donaldo Meynard Tom Beeckman Michael Gomez Selvaraj Ishitani Manabu Anna-Maria Genga Christophe Brugidou Vinh Nang Do Emmanuel Guiderdoni Jean-Benoit Morel Pascal Gantet 《Plant physiology》2015,169(4):2935-2949
125.
Numerical information can be conveyed by either symbolic or nonsymbolic representation. Some symbolic numerals can also be identified as nonsymbolic quantities defined by the number of lines (e.g., I, II, III in Roman and -, =, ≡ in Japanese Kanji and Chinese). Here we report that such multi-representation of magnitude can facilitate the processing of these numerals under certain circumstances. In a magnitude comparison task judging 1 to 9 (except 5) Chinese and Arabic numerals presented at the foveal (at the center) or parafoveal (3° left or right of the center) location, multi-representational small-value Chinese numerals showed a processing advantage over single-representational Arabic numerals and large-value Chinese numerals only in the parafoveal condition, demonstrated by lower error rates and faster reaction times. Further event-related potential (ERP) analysis showed that such a processing advantage was not reflected by traditional ERP components identified in previous studies of number processing, such as N1 or P2p. Instead, the difference was found much later in a N400 component between 300-550 msec over parietal regions, suggesting that those behavioral differences may not be due to early processing of visual identification, but later processing of subitizing or accessing mental number line when lacking attentional resources. These results suggest that there could be three stages of number processing represented separately by the N1, P2p and N400 ERP components. In addition, numerical information can be represented simultaneously by both symbolic and nonsymbolic systems, which will facilitate number processing in certain situations. 相似文献
126.
Malling-Merton 106 apple rootstocks inoculated with Pratylenchus penetrans, or uninoculated, were grown in a growth chamber in pots of loamy sand maintained at two moisture levels, 0 to -0.4 bar or 0 to -10 bars. Either inoculation or low soil moisture suppressed shoot growth and increased root necrosis. However, the nematode-soil moisture interaction was not significant. 相似文献
127.
Nguyen Thi Quynh Mai Nguyen Thi Kim Thu Le Dac Tuyen Truong Chi Lam Vu Dinh Lam Nguyen Thi Quynh Hoa 《Plasmonics (Norwell, Mass.)》2021,16(5):1583-1592
Plasmonics - Developing a simple structure using low-cost material that enables both large-scale fabrication and broadband absorption response is highly desirable but very challenging for achieving... 相似文献
128.
Takahashi Yumiko Sarkar Juli Yamada Jumpei Matsunaga Yutaka Nonaka Yudai Banjo Mai Sakaguchi Ryo Shinya Terunaga Hatta Hideo 《Journal of physiology and biochemistry》2021,77(3):469-480
Journal of Physiology and Biochemistry - To identify factors that influence post-exercise muscle glycogen repletion, we compared the glycogen recovery after level running with downhill running, an... 相似文献
129.
130.