排序方式: 共有87条查询结果,搜索用时 15 毫秒
21.
David Razafsky Candace Ward Chloe Potter Wanqiu Zhu Yunlu Xue Vladimir J. Kefalov Loren G. Fong Stephen G. Young Didier Hodzic 《Molecular biology of the cell》2016,27(12):1928-1937
Lamin B1 and lamin B2 are essential building blocks of the nuclear lamina, a filamentous meshwork lining the nucleoplasmic side of the inner nuclear membrane. Deficiencies in lamin B1 and lamin B2 impair neurodevelopment, but distinct functions for the two proteins in the development and homeostasis of the CNS have been elusive. Here we show that embryonic depletion of lamin B1 in retinal progenitors and postmitotic neurons affects nuclear integrity, leads to the collapse of the laminB2 meshwork, impairs neuronal survival, and markedly reduces the cellularity of adult retinas. In stark contrast, a deficiency of lamin B2 in the embryonic retina has no obvious effect on lamin B1 localization or nuclear integrity in embryonic retinas, suggesting that lamin B1, but not lamin B2, is strictly required for nucleokinesis during embryonic neurogenesis. However, the absence of lamin B2 prevents proper lamination of adult retinal neurons, impairs synaptogenesis, and reduces cone photoreceptor survival. We also show that lamin B1 and lamin B2 are extremely long-lived proteins in rod and cone photoreceptors. OF interest, a complete absence of both proteins during postnatal life has little or no effect on the survival and function of cone photoreceptors. 相似文献
22.
David Ochoa Mindaugas Jonikas Robert T Lawrence Bachir El Debs Joel Selkrig Athanasios Typas Judit Villén Silvia DM Santos Pedro Beltrao 《Molecular systems biology》2016,12(12)
The coordinated regulation of protein kinases is a rapid mechanism that integrates diverse cues and swiftly determines appropriate cellular responses. However, our understanding of cellular decision‐making has been limited by the small number of simultaneously monitored phospho‐regulatory events. Here, we have estimated changes in activity in 215 human kinases in 399 conditions derived from a large compilation of phosphopeptide quantifications. This atlas identifies commonly regulated kinases as those that are central in the signaling network and defines the logic relationships between kinase pairs. Co‐regulation along the conditions predicts kinase–complex and kinase–substrate associations. Additionally, the kinase regulation profile acts as a molecular fingerprint to identify related and opposing signaling states. Using this atlas, we identified essential mediators of stem cell differentiation, modulators of Salmonella infection, and new targets of AKT1. This provides a global view of human phosphorylation‐based signaling and the necessary context to better understand kinase‐driven decision‐making. 相似文献
23.
Variations among cell lines in the synthesis of sphingolipids in de novo and recycling pathways 总被引:1,自引:0,他引:1
There are several pathways for the incorporation of sugars into
glycosphingolipids (GSL). Sugars can be added to ceramide that contains
sphinganine (dihydrosphingosine) synthesized de novo (pathway 1), to
ceramide synthesized from sphingoid bases produced by hydrolysis of
sphingolipids (pathway 2), and into GSL recycling from the endosomal
pathway through the Golgi (pathway 3). We reported previously the
surprising observation that SW13 cells, a human adrenal carcinoma cell
line, synthesize most of their GSL in pathway 2. We now present data on the
synthesis of GSL in four additional cell lines. Approximately 90% of sugar
incorporation took place in pathway 2, and 10% or less in pathway 1, in
human foreskin fibroblasts and NB41A3 neuroblastoma cells. In contrast,
approximately 50-90% of sugar incorporation took place in pathway 1 in
C2C12 myoblasts. The C2C12 cells divide more rapidly and synthesize 10-14
times as much GSL as the other three cell lines. In C6 glioma cells,
approximately 30% of sugar incorporation occurred in pathway 1 and 60% in
pathway 2. There was no relation between the utilization of pathways for
GSL and sphingomyelin synthesis in foreskin fibroblasts and C2C12 cells. In
both cells pathways 1 and 2 each accounted for 50% of incorporation of
choline into sphingomyelin. In five of the six cell lines that we have
studied, most GSL synthesis takes place in pathway 2. We suggest that when
the need for synthesis is relatively low, as in slowly dividing cells, GSL
are synthesized predominantly from sphingoid bases salvaged from the
hydrolytic pathway. When cells are dividing more rapidly, the need for
increased synthesis is met by upregulating the de novo pathway.
相似文献
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25.
Crisp M Liu Q Roux K Rattner JB Shanahan C Burke B Stahl PD Hodzic D 《The Journal of cell biology》2006,175(1):41-53
The nuclear envelope defines the barrier between the nucleus and cytoplasm and features inner and outer membranes separated by a perinuclear space (PNS). The inner nuclear membrane contains specific integral proteins that include Sun1 and Sun2. Although the outer nuclear membrane (ONM) is continuous with the endoplasmic reticulum, it is nevertheless enriched in several integral membrane proteins, including nesprin 2 Giant (nesp2G), an 800-kD protein featuring an NH(2)-terminal actin-binding domain. A recent study (Padmakumar, V.C., T. Libotte, W. Lu, H. Zaim, S. Abraham, A.A. Noegel, J. Gotzmann, R. Foisner, and I. Karakesisoglou. 2005. J. Cell Sci. 118:3419-3430) has shown that localization of nesp2G to the ONM is dependent upon an interaction with Sun1. In this study, we confirm and extend these results by demonstrating that both Sun1 and Sun2 contribute to nesp2G localization. Codepletion of both of these proteins in HeLa cells leads to the loss of ONM-associated nesp2G, as does overexpression of the Sun1 lumenal domain. Both treatments result in the expansion of the PNS. These data, together with those of Padmakumar et al. (2005), support a model in which Sun proteins tether nesprins in the ONM via interactions spanning the PNS. In this way, Sun proteins and nesprins form a complex that links the nucleoskeleton and cytoskeleton (the LINC complex). 相似文献
26.
Patr��cia F N Fa��sca Ana Nunes Rui DM Travasso Eugene I Shakhnovich 《Protein science : a publication of the Protein Society》2010,19(11):2196-2209
Systematic Monte Carlo simulations of simple lattice models show that the final stage of protein folding is an ordered process where native contacts get locked (i.e., the residues come into contact and remain in contact for the duration of the folding process) in a well‐defined order. The detailed study of the folding dynamics of protein‐like sequences designed as to exhibit different contact energy distributions, as well as different degrees of sequence optimization (i.e., participation of non‐native interactions in the folding process), reveals significant differences in the corresponding locking scenarios—the collection of native contacts and their average locking times, which are largely ascribable to the dynamics of non‐native contacts. Furthermore, strong evidence for a positive role played by non‐native contacts at an early folding stage was also found. Interestingly, for topologically simple target structures, a positive interplay between native and non‐native contacts is observed also toward the end of the folding process, suggesting that non‐native contacts may indeed affect the overall folding process. For target models exhibiting clear two‐state kinetics, the relation between the nucleation mechanism of folding and the locking scenario is investigated. Our results suggest that the stabilization of the folding transition state can be achieved through the establishment of a very small network of native contacts that are the first to lock during the folding process. 相似文献
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28.
Background
The statistical modeling of biomedical corpora could yield integrated, coarse-to-fine views of biological phenomena that complement discoveries made from analysis of molecular sequence and profiling data. Here, the potential of such modeling is demonstrated by examining the 5,225 free-text items in the Caenorhabditis Genetic Center (CGC) Bibliography using techniques from statistical information retrieval. Items in the CGC biomedical text corpus were modeled using the Latent Dirichlet Allocation (LDA) model. LDA is a hierarchical Bayesian model which represents a document as a random mixture over latent topics; each topic is characterized by a distribution over words. 相似文献29.
Background
The shape of phylogenetic trees has been used to make inferences about the evolutionary process by comparing the shapes of actual phylogenies with those expected under simple models of the speciation process. Previous studies have focused on speciation events, but gene duplication is another lineage splitting event, analogous to speciation, and gene loss or deletion is analogous to extinction. Measures of the shape of gene family phylogenies can thus be used to investigate the processes of gene duplication and loss. We make the first systematic attempt to use tree shape to study gene duplication using human gene phylogenies. 相似文献30.
Brian?DM?TomEmail author Walter?R?Gilks Elizabeth?T?Brooke-Powell James?W?Ajioka 《BMC bioinformatics》2005,6(1):234