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21.
Chromosomal Proteins and Cytokinesis: Patterns of Cleavage Furrow Formation and Inner Centromere Protein Positioning in Mitotic Heterokaryons and Mid-anaphase Cells 总被引:9,自引:1,他引:8 下载免费PDF全文
D. Mark Eckley Alexandra M. Ainsztein Alastair M. Mackay Ilya G. Goldberg William C. Earnshaw 《The Journal of cell biology》1997,136(6):1169-1183
After the separation of sister chromatids in anaphase, it is essential that the cell position a cleavage furrow so that it partitions the chromatids into two daughter cells of roughly equal size. The mechanism by which cells position this cleavage furrow remains unknown, although the best current model is that furrows always assemble midway between asters. We used micromanipulation of human cultured cells to produce mitotic heterokaryons with two spindles fused in a V conformation. The majority (15/19) of these cells cleaved along a single plane that transected the two arms of the V at the position where the metaphase plate had been, a result at odds with current views of furrow positioning. However, four cells did form an additional ectopic furrow between the spindle poles at the open end of the V, consistent with the established view. To begin to address the mechanism of furrow assembly, we have begun a detailed study of the properties of the chromosome passenger inner centromere protein (INCENP) in anaphase and telophase cells. We found that INCENP is a very early component of the cleavage furrow, accumulating at the equatorial cortex before any noticeable cortical shape change and before any local accumulation of myosin heavy chain. In mitotic heterokaryons, INCENP was detected in association with spindle midzone microtubules beneath sites of furrowing and was not detected when furrows were absent. A functional role for INCENP in cytokinesis was suggested in experiments where a nearly full-length INCENP was tethered to the centromere. Many cells expressing the chimeric INCENP failed to complete cytokinesis and entered the next cell cycle with daughter cells connected by a large intercellular bridge with a prominent midbody. Together, these results suggest that INCENP has a role in either the assembly or function of the cleavage furrow. 相似文献
22.
Andrea Robitzki Alexandra Mack Arnaud Chatonnet Paul G. Layer 《Journal of neurochemistry》1997,69(2):823-833
Abstract: The function of the enzyme butyrylcholinesterase (BChE) in the developing and mature brain is still unclear. We have inserted 577 bp of the 5' upstream region plus 106 bp of the exon 1 of the rabbit BChE gene in reverse orientation under control of an SV40 early promoter derivative in an expression vector. This vector was introduced by calcium phosphate-mediated transfection into embryonic chicken retina cells during the first days of reaggregation culture. Depending on the retinal origin, the transfected cell population forms histotypic retina-like spheres, so-called rosetted or stratified retinospheroids. We show that antisense 5'-BChE gene expression decreased the steady-state mRNA level of BChE and the translation of the BChE protein, inhibited proliferation, and accelerated histogenesis in both cellular systems. The pronounced effects of antisense 5'-BChE transfection of spheroids document a key role of BChE during the early reaggregation process of retinal cells, most likely by regulating their growth and differentiation. 相似文献
23.
Nathalie Doerflinger Catherine Linder Karim Ouahchi Gabor Gyapay Jean Weissenbach Denis Le Paslier Philippe Rigault Samir Belal Christiane Ben Hamida Faycal Hentati Mongi Ben Hamida Massimo Pandolfo Stephano DiDonato Ronald Sokol Herbert Kayden Pierre Landrieu Alexandra Durr Alexis Brice Fran?oise Goutières Alfried Kohlschütter Pascal Sabouraud Ali Benomar Mohamed Yahyaoui Jean-Louis Mandel Michel Koenig 《American journal of human genetics》1995,56(5):1116-1124
Ataxia with vitamin E deficiency (AVED) is an autosomal recessive disease characterized clinically by neurological symptoms with often striking resemblance to those of Friedreich ataxia. This disorder has been reported previously as familial isolated vitamin E deficiency. We have mapped recently the AVED locus to a 5-cM confidence interval on chromosome 8q by homozygosity mapping in six Mediterranean families. We have now analyzed six new and two previously described families and demonstrate genetic homogeneity despite important clinical variability and wide geographic origins. Analysis of nine new tightly linked microsatellite markers, including four characterized in this study, revealed a predominant but not unique mutation in northern African populations, where this condition is more frequent. Haplotype analysis but also classical recombinations allowed us to refine the AVED position to a 1-cM interval. A YAC contig over this interval was constructed from marker STSs and YAC fingerprint data, in order to facilitate the search of the AVED gene. 相似文献
24.
Evidence for a major gene (RP10) for autosomal dominant retinitis pigmentosa on chromosome 7q: linkage mapping in a second,unrelated family 总被引:7,自引:0,他引:7
Rachel E. McGuire Alexandra M. Gannon Lori S. Sullivan Joseph A. Rodriguez Stephen P. Daiger 《Human genetics》1995,95(1):71-74
Retinitis pigmentosa is a genetically heterogeneous form of retinal degeneration, which has X-linked, autosomal recessive and autosomal dominant forms. The disease genes in families with autosomal dominant retinitis pigmentosa (adRP) have been linked to six loci, on 3q, 6p, 7p, 7q, 8q and 19q. In a large American family with late-onset adRP, microsatellite markers were used to test for linkage to the loci on 3q, 6p, 7p, 7q and 8q. Linkage was found to 7q using the marker D7S480. Additional microsatellite markers from 7q were then tested. In total, five markers, D7S480, D7S514, D7S633, D7S650 and D7S677, show statistically significant evidence for link-age in this family, with a maximum two-point lod score of 5.3 at 0% recombination from D7S514. These results confirm an earlier report of linkage to an adRP locus (RP10) in an unrelated family of Spanish origin and indicate that RP10 may be a significant gene for inherited retinal degeneration. In addition, we used recently reported microsatellite markers from 7q to refine the linkage map of the RP10 locus. 相似文献
25.
Background: Protein kinase Cs are a family of enzymes that transduce the plethora of signals promoting lipid hydrolysis. Here, we show that protein kinase C must first be processed by three distinct phosphorylations before it is competent to respond to second messengers.Results We have identified the positions and functions of the in vivo phosphorylation sites of protein kinase C by mass spectrometry and peptide sequencing of native and phosphatase-treated kinase from the detergent-soluble fraction of cells. Specifically, the threonine at position 500 (T500) on the activation loop, and T641 and S660 on the carboxyl terminus of protein kinase C βII are phosphorylated in vivo. T500 and S660 are selectively dephosphorylated in vitro by protein phosphatase 2A to yield an enzyme that is still capable of lipid-dependent activation, whereas all three residues are dephosphorylated by protein phosphatase 1 to yield an inactive enzyme. Biochemical analysis reveals that protein kinase C autophosphorylates on S660, that autophosphorylation on S660 follows T641 autophosphorylation, that autophosphorylation on S660 is accompanied by the release of protein kinase C into the cytosol, and that T500 is not an autophosphorylation site.Conclusion Structural and biochemical analyses of native and phosphatase-treated protein kinase C indicate that protein kinase C is processed by three phosphorylations. Firstly, trans-phosphorylation on the activation loop (T500) renders it catalytically competent to autophosphorylate. Secondly, a subsequent autophosphorylation on the carboxyl terminus (T641) maintains catalytic competence. Thirdly, a second autophosphorylation on the carboxyl terminus (S660) regulates the enzyme's subcellular localization. The conservation of each of these residues (or an acidic residue) in conventional, novel and atypical protein kinase Cs underscores the essential role for each in regulating the protein kinase C family. 相似文献
26.
Alexandra Shedlovsky Linda J. Clipson John L. VandeBerg William F. Dove 《Immunogenetics》1981,13(5):413-419
Evidence is presented for the existence of two strong murine teratocarcinoma transplantation antigens (Gt) on the cell line PCC3. It is shown that the loci governing expression of these antigens are linked to the H-2 complex. These loci have been further mapped with respect to the brachyury marker (T) and H-2: Gt-1 lies 5±2 crossover units proximal to H-2 and 12±2 crossover units distal to T, Gt-2 lies 21±4 crossover units distal to H-2. It is possible that these strong transplantation antigens provide an embryonic analogue to the adult major histocompatibility system. 相似文献
27.
Cleavage of Bovine Brain Microtubule-Associated Protein-2 by Human Immunodeficiency Virus Proteinase
The high-molecular-weight dendritic cytoskeletal protein known as microtubule-associated protein (MAP)-2 displays the capacity to stimulate tubulin polymerization and to associate with microtubules. Serine proteases cleave MAP-2 into a C-terminal M(r) 28,000-35,000 microtubule-binding fragment and a larger N-terminal M(r) 240,000 projection-arm region. We now show that human immunodeficiency virus (HIV) proteinase also progressively degrades purified MAP-2 in vitro. This proteolysis reaction is characterized by transient accumulation of at least six intermediates, and most abundant of these is an M(r) 72,000 species that retains the ability to associate with taxol-stabilized microtubules. Treatment of this M(r) 72,000 species with thrombin releases the same M(r) 28,000 component as that derived from thrombin action on intact high-molecular-weight MAP-2, indicating that the viral aspartoproteinase action preferentially occurs further toward the N-terminus. The association of the M(r) 72,000 component with microtubules can be disrupted by the presence of a 21-amino acid peptide analogue of the second repeated sequence in the MAP-2 microtubule-binding region. We also studied HIV proteinase action on MAP-2 in the presence of tubulin and other MAPs that recycle with tubulin, and contrary to other published studies we found no effect of such treatment on microtubule self-assembly behavior. Cleavage of isolated MAP-2 by the HIV enzyme at high salt concentrations, followed by desalting and addition of tubulin, also resulted in microtubule assembly, albeit with slightly reduced efficiency. 相似文献
28.
Victor Rico-Gray Jose G. Garcia-Franco Alexandra Chemas Armando Puch Paulino Sima 《Economic botany》1990,44(4):470-487
We studied species composition, similarity, and structure of homegardens in two Yucatecan Maya communities, Tixpeual and Tixcacaltuyub, Yucatan, Mexico. The number of gardens sampled per village was 20 and 22; total area sampled was very similar, 45,265 m2 and 40,150 m2; the number of trees and shrubs present was 5651 and 5603; and number of species was 135 and 133, respectively. Diversity was low for both sites (H′= 1.6), as were the correlation coefficients (r) for the species-area and individuals-area correlations. The relatively low values obtained for the structural parameters reflect the random pattern of plant incorporation to the gardens, the variability in the proportion of constantly used and not constantly used garden area, and a certain uniformity in the number of species used and number of individuals present, and the relationship between these parameters and garden size. All these reflect the uniqueness of each homegarden, which depends upon the cultural background of the owner. We noticed a trend towards a change in homegarden structure and function in response to the modernization process. Homegardens in villages in the outskirts of cities tend to have more ornamental species and commercial fruit plants than homegardens in isolated villages. 相似文献
29.
30.
Alexandra R Dvorscek Craig I McKenzie Marcus J Robinson Zhoujie Ding Catherine Pitt Kristy O'Donnell Dimitra Zotos Robert Brink David M Tarlinton Isaak Quast 《EMBO reports》2022,23(9)
The proliferation and differentiation of antigen‐specific B cells, including the generation of germinal centers (GC), are prerequisites for long‐lasting, antibody‐mediated immune protection. Affinity for antigen determines B cell recruitment, proliferation, differentiation, and competitiveness in the response, largely through determining access to T cell help. However, how T cell‐derived signals contribute to these outcomes is incompletely understood. Here, we report how the signature cytokine of follicular helper T cells, IL‐21, acts as a key regulator of the initial B cell response by accelerating cell cycle progression and the rate of cycle entry, increasing their contribution to the ensuing GC. This effect occurs over a wide range of initial B cell receptor affinities and correlates with elevated AKT and S6 phosphorylation. Moreover, the resultant increased proliferation can explain the IL‐21‐mediated promotion of plasma cell differentiation. Collectively, our data establish that IL‐21 acts from the outset of a T cell‐dependent immune response to increase cell cycle progression and fuel cyclic re‐entry of B cells, thereby regulating the initial GC size and early plasma cell output. 相似文献