Cell motility and the cytoskeleton最新文献

{"title":"The betaII isotype of tubulin is present in the cell nuclei of a variety of cancers.","authors":"I-Tien Yeh,&nbsp;Richard F Ludueña","doi":"10.1002/cm.10157","DOIUrl":"https://doi.org/10.1002/cm.10157","url":null,"abstract":"<p><p>Tubulin, the subunit protein of microtubules, has generally been thought to be exclusively a cytoplasmic protein in higher eukaryotes. We have previously shown that cultured rat kidney mesangial cells contain the betaII isotype of tubulin in their nuclei in the form of an alphabetaII dimer [Walss et al., 1999: Cell Motil. Cytoskeleton 42:274-284, 1999]. More recently, we examined a variety of cancerous and non-cancerous cell lines and found betaII in the nuclei of all of the former and only a few of the latter (Walss-Bass et al., 2002: Cell Tissue Res. 308:215-223]. In order to determine if betaII-tubulin occurs in the nuclei of actual cancers as well as in cancer cell lines, we used the immunoperoxidase method to look for nuclear betaII in a variety of tumors excised from 201 patients. We found that 75% of these tumors contain betaII in their nuclei. Distribution of nuclear betaII was highly dependent on the type of cancer, with 100% of the colon and prostate cancers, but only 19% of the skin tumors, having nuclear betaII. Nuclear betaII was particularly marked in tumors of epithelial origin, of which 83% showed nuclear betaII, in contrast to 54% in tumors of non-epithelial origin. In many cases, betaII staining occurred very strongly in the nuclei and not in the cytoplasm; in other cases, betaII was present in both. In many cases, particularly metastases, otherwise normal cells adjacent to the tumor also showed nuclear betaII, suggesting that cancer cells may influence nearby cells to synthesize betaII and localize it to their nuclei. Our results have implications for the diagnosis, biology, and chemotherapy of cancer.</p>","PeriodicalId":9675,"journal":{"name":"Cell motility and the cytoskeleton","volume":"57 2","pages":"96-106"},"PeriodicalIF":0.0,"publicationDate":"2004-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/cm.10157","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24138876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aneuploidy, the somatic mutation that makes cancer a species of its own.","authors":"P Duesberg,&nbsp;D Rasnick","doi":"10.1002/1097-0169(200010)47:2<81::AID-CM1>3.0.CO;2-#","DOIUrl":"https://doi.org/10.1002/1097-0169(200010)47:2<81::AID-CM1>3.0.CO;2-#","url":null,"abstract":"<p><p>The many complex phenotypes of cancer have all been attributed to \"somatic mutation.\" These phenotypes include anaplasia, autonomous growth, metastasis, abnormal cell morphology, DNA indices ranging from 0.5 to over 2, clonal origin but unstable and non-clonal karyotypes and phenotypes, abnormal centrosome numbers, immortality in vitro and in transplantation, spontaneous progression of malignancy, as well as the exceedingly slow kinetics from carcinogen to carcinogenesis of many months to decades. However, it has yet to be determined whether this mutation is aneuploidy, an abnormal number of chromosomes, or gene mutation. A century ago, Boveri proposed cancer is caused by aneuploidy, because it correlates with cancer and because it generates \"pathological\" phenotypes in sea urchins. But half a century later, when cancers were found to be non-clonal for aneuploidy, but clonal for somatic gene mutations, this hypothesis was abandoned. As a result aneuploidy is now generally viewed as a consequence, and mutated genes as a cause of cancer although, (1) many carcinogens do not mutate genes, (2) there is no functional proof that mutant genes cause cancer, and (3) mutation is fast but carcinogenesis is exceedingly slow. Intrigued by the enormous mutagenic potential of aneuploidy, we undertook biochemical and biological analyses of aneuploidy and gene mutation, which show that aneuploidy is probably the only mutation that can explain all aspects of carcinogenesis. On this basis we can now offer a coherent two-stage mechanism of carcinogenesis. In stage one, carcinogens cause aneuploidy, either by fragmenting chromosomes or by damaging the spindle apparatus. In stage two, ever new and eventually tumorigenic karyotypes evolve autocatalytically because aneuploidy destabilizes the karyotype, ie. causes genetic instability. Thus, cancer cells derive their unique and complex phenotypes from random chromosome number mutation, a process that is similar to regrouping assembly lines of a car factory and is analogous to speciation. The slow kinetics of carcinogenesis reflects the low probability of generating by random chromosome reassortments a karyotype that surpasses the viability of a normal cell, similar again to natural speciation. There is correlative and functional proof of principle: (1) solid cancers are aneuploid; (2) genotoxic and non-genotoxic carcinogens cause aneuploidy; (3) the biochemical phenotypes of cells are severely altered by aneuploidy affecting the dosage of thousands of genes, but are virtually un-altered by mutations of known hypothetical oncogenes and tumor suppressor genes; (4) aneuploidy immortalizes cells; (5) non-cancerous aneuploidy generates abnormal phenotypes in all species tested, e.g., Down syndrome; (6) the degrees of aneuploidies are proportional to the degrees of abnormalities in non-cancerous and cancerous cells; (7) polyploidy also varies biological phenotypes; (8) variation of the numbers of chromosomes is the basis","PeriodicalId":9675,"journal":{"name":"Cell motility and the cytoskeleton","volume":"47 2","pages":"81-107"},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1097-0169(200010)47:2<81::AID-CM1>3.0.CO;2-#","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21845893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vigorous beating of Chlamydomonas axonemes lacking central pair/radial spoke structures in the presence of salts and organic compounds.","authors":"T Yagi,&nbsp;R Kamiya","doi":"10.1002/1097-0169(200007)46:3<190::AID-CM4>3.0.CO;2-#","DOIUrl":"https://doi.org/10.1002/1097-0169(200007)46:3<190::AID-CM4>3.0.CO;2-#","url":null,"abstract":"<p><p>Flagella of Chlamydomonas mutants lacking the central pair of microtubules or radial spokes do not beat; however, axonemes isolated from these mutants were found to display vigorous bending movements in the presence of ATP and various salts, sugars, alcohols, and other organic compounds. For example, about 15% of the total axonemes isolated from pf18, a mutant lacking the central pair, displayed beating in the presence of 10 mM MgSO(4) and 0.2 mM ATP at about 22 Hz, while none beat with the same concentration of ATP and < or = 5 mM or > or = 25 mM MgSO(4). The beat frequency and waveform of beating pf18 axonemes were similar to those of wild type axonemes beating under the same conditions. Similarly, 10-50% of the axonemes beat in the presence of 0.5 M sucrose, 2.0 M glycerol, or 1.7 M[10% (v/v)] ethanol. The appearance of motility did not correlate with the change in axonemal ATPase; however, these substances at those concentrations commonly increased the amplitude of nanometer-scale oscillation (hyper-oscillation) in pf18 axonemes, as well as the extent of ATP-induced sliding disintegration of protease-treated axonemes. Axonemes of double mutants lacking both the central pair and various subspecies of inner-arm dynein also beat at increased MgSO(4) concentrations, but axonemes lacking outer-arm dynein in addition to the central pair did not beat. These and other observations suggest that small molecules perturb the regulation of microtubule sliding through some change in water activity or osmotic stress. Axonemes must have an intrinsic ability to beat without the central pair/radial spokes under a variety of non-physiological solution conditions, as long as the outer dynein arms are present. Apparently, the major function of the central pair/radial spoke structures is to restore this activity under physiological conditions.</p>","PeriodicalId":9675,"journal":{"name":"Cell motility and the cytoskeleton","volume":"46 3","pages":"190-9"},"PeriodicalIF":0.0,"publicationDate":"2000-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/1097-0169(200007)46:3<190::AID-CM4>3.0.CO;2-#","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21754167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Forced expression of a dominant-negative chimeric tropomyosin causes abnormal motile behavior during cell division.","authors":"K Wong,&nbsp;D Wessels,&nbsp;S L Krob,&nbsp;A R Matveia,&nbsp;J L Lin,&nbsp;D R Soll,&nbsp;J J Lin","doi":"10.1002/(SICI)1097-0169(200002)45:2<121::AID-CM4>3.0.CO;2-#","DOIUrl":"https://doi.org/10.1002/(SICI)1097-0169(200002)45:2<121::AID-CM4>3.0.CO;2-#","url":null,"abstract":"<p><p>Forced expression of the chimeric human fibroblast tropomyosin 5/3 (hTM5/3) in CHO cell was previously shown to affect cytokinesis [Warren et al., 1995: J. Cell Biol. 129:697-708]. To further investigate the phenotypic consequences of misexpression, we have compared mitotic spindle organization and dynamic 2D and 3D shape changes during mitosis in normal cells and in a hTM5/3 misexpressing (mutant) cell line. Immunofluorescence microscopy of wild type and mutant cells stained with monoclonal anti-tubulin antibody revealed that the overall structures of mitotic spindles were not significantly different. However, the axis of the mitotic spindle in mutant cells was more frequently misaligned with the long axis of the cell than that of wild type cells. To assess behavioral differences during mitosis, wild type and mutant cells were reconstructed in 2D and 3D and motion analyzed with the computer-assisted 2D and 3D Dynamic Image Analysis Systems (2D-DIAS, 3D-DIAS). Mutant cells abnormally formed large numbers of blebs during the later stages of mitosis and took longer to proceed from the start of anaphase to the start of cytokinesis. Furthermore, each mutant cell undergoing mitosis exhibited greater shape complexity than wild type cells, and in every case lifted one of the two evolving daughter cells off the substratum and abnormally twisted. These results demonstrate that misexpression of hTM5/3 in CHO cells leads to morphological instability during mitosis. Misexpression of hTM5/3 interferes with normal tropomyosin function, suggesting in turn that tropomyosin plays a role through its interaction with actin microfilaments in the regulation of the contractile ring, in the localized suppression of blebbing, in the maintenance of polarity and spatial symmetry during cytokinesis, and in cell spreading after cytokinesis is complete.</p>","PeriodicalId":9675,"journal":{"name":"Cell motility and the cytoskeleton","volume":"45 2","pages":"121-32"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/(SICI)1097-0169(200002)45:2<121::AID-CM4>3.0.CO;2-#","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21513378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Movement of turritella spermatozoa: direction of propagation and chirality of flagellar bends.","authors":"S Ishijima,&nbsp;S A Ishijima,&nbsp;B A Afzelius","doi":"10.1002/(SICI)1097-0169(199910)44:2<85::AID-CM1>3.0.CO;2-#","DOIUrl":"https://doi.org/10.1002/(SICI)1097-0169(199910)44:2<85::AID-CM1>3.0.CO;2-#","url":null,"abstract":"<p><p>The marine snail, Turritella communis, produces two types of spermatozoa, named apyrene and eupyrene. Eupyrene spermatozoa are usually paired, but unpaired ones are involved in fertilization. Movements of these spermatozoa were analyzed using a video camera with a high-speed shutter. The eupyrene spermatozoa usually swim with the head foremost but are able to swim flagellum foremost. A reversal of the direction of their swimming was found to be the result of a change in the direction of flagellar bend propagation, which changed with calcium concentration. Reversal of the direction of bend propagation was accompanied by a reversal of direction of the rotational movement of the spermatozoa around their long axis, suggesting that the bending waves keep the sense of their three-dimensional form. The swimming speed of apyrene spermatozoa in natural seawater was about one-eighth of that of the eupyrene ones and remained almost constant in highly viscous medium. The swimming speed of conjugated eupyrene spermatozoa was the same as that of unpaired spermatozoa over a wide viscosity range (<3,000 cP). No advantage of swimming by two spermatozoa could be detected in Turritella spermatozoa.</p>","PeriodicalId":9675,"journal":{"name":"Cell motility and the cytoskeleton","volume":"44 2","pages":"85-95"},"PeriodicalIF":0.0,"publicationDate":"1999-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/(SICI)1097-0169(199910)44:2<85::AID-CM1>3.0.CO;2-#","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21370500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microtubule severing.","authors":"L. Quarmby, T. A. Lohret","doi":"10.1002/(sici)1097-0169(1999)43:1<1::aid-cm1>3.0.co;2-","DOIUrl":"https://doi.org/10.1002/(sici)1097-0169(1999)43:1<1::aid-cm1>3.0.co;2-","url":null,"abstract":"The regulation of microtubule stability by severing of the polymer along its length is a newly appreciated and potentially important mechanism for controlling microtubule function. Microtubule severing occurs in living cells, but direct observation of this event is infrequent. The paucity of direct observations leave open to question the significance of regulated microtubule severing in the control of microtubule organization. Nevertheless, several lines of evidence suggest that microtubule severing is an important cellular activity. First, the ATP-dependent microtubule-severing activity of katanin is well documented. Katanin is found in most cell types and is enriched at MTOCs. Although it is possible that katanin does not sever microtubules in vivo, this seems unlikely. Second, a physiological event, deflagellation, has been shown to depend on microtubule severing. The deflagellation system of Chlamydomonas has provided a genetic approach to the problem of microtubule severing. The FA genes are essential for the regulated severing of axonemal microtubules during deflagellation, but whether these genes define new severing proteins or whether they are important for katanin activity remains to be determined. Microtubule severing is a relatively new area of investigation and there are still many more questions than answers. It is anticipated that the recent cloning of katanin and the introduction of a genetic model system will soon lead to significant breakthroughs in this problem.","PeriodicalId":9675,"journal":{"name":"Cell motility and the cytoskeleton","volume":"21 3","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50667466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microtubule severing.","authors":"L M Quarmby,&nbsp;T A Lohret","doi":"10.1002/(SICI)1097-0169(1999)43:1<1::AID-CM1>3.0.CO;2-#","DOIUrl":"https://doi.org/10.1002/(SICI)1097-0169(1999)43:1<1::AID-CM1>3.0.CO;2-#","url":null,"abstract":"<p><p>The regulation of microtubule stability by severing of the polymer along its length is a newly appreciated and potentially important mechanism for controlling microtubule function. Microtubule severing occurs in living cells, but direct observation of this event is infrequent. The paucity of direct observations leave open to question the significance of regulated microtubule severing in the control of microtubule organization. Nevertheless, several lines of evidence suggest that microtubule severing is an important cellular activity. First, the ATP-dependent microtubule-severing activity of katanin is well documented. Katanin is found in most cell types and is enriched at MTOCs. Although it is possible that katanin does not sever microtubules in vivo, this seems unlikely. Second, a physiological event, deflagellation, has been shown to depend on microtubule severing. The deflagellation system of Chlamydomonas has provided a genetic approach to the problem of microtubule severing. The FA genes are essential for the regulated severing of axonemal microtubules during deflagellation, but whether these genes define new severing proteins or whether they are important for katanin activity remains to be determined. Microtubule severing is a relatively new area of investigation and there are still many more questions than answers. It is anticipated that the recent cloning of katanin and the introduction of a genetic model system will soon lead to significant breakthroughs in this problem.</p>","PeriodicalId":9675,"journal":{"name":"Cell motility and the cytoskeleton","volume":"43 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/(SICI)1097-0169(1999)43:1<1::AID-CM1>3.0.CO;2-#","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21210800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fertilization and pronuclear migration in the ctenophore, Beroe ovata. Video supplement.","authors":"C Rouvière,&nbsp;E Houliston,&nbsp;D Carré,&nbsp;P Chang,&nbsp;C Sardet","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9675,"journal":{"name":"Cell motility and the cytoskeleton","volume":"39 4","pages":"340-2"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20478888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The ankyrin-binding domain of CD44s is involved in regulating hyaluronic acid-mediated functions and prostate tumor cell transformation.","authors":"D. Zhu, L. Bourguignon","doi":"10.1002/(SICI)1097-0169(1998)39:3<209::AID-CM4>3.0.CO;2","DOIUrl":"https://doi.org/10.1002/(SICI)1097-0169(1998)39:3<209::AID-CM4>3.0.CO;2","url":null,"abstract":"CD44 isoforms, such as CD44s (the standard form), contain at least one ankyrin-binding site within the 70-amino acid (aa) cytoplasmic domain and several hyaluronic acid (HA)-binding sites within the extracellular domain. To study the role of CD44s-ankyrin interaction in regulating human prostate tumor cells, we have constructed several CD44s cytoplasmic deletion mutants that lack the ankyrin-binding site(s). These truncated cDNAs were stably transfected into CD44-negative human prostate tumor cells (LNCaP). Our results indicate that a critical region of 15-amino acids (aa) between aa 304 and aa 318 of CD44s is required for ankyrin binding. Biochemical analyses, using competition binding assays with a synthetic peptide containing the 15 aa between aa 304 and aa 318 (NSGNGAVEDRKPSGL), further support the conclusion that this region contains the ankyrin-binding domain of CD44s. Deletion of this 15-aa ankyrin-binding sequence from CD44s results in a drastic reduction of HA-mediated binding/cell adhesion, Src p60 kinase(s) interaction and anchorage-independent growth in soft agar. These findings suggest that the binding of cytoskeletal proteins, such as ankyrin, to the cytoplasmic domain of CD44s plays a pivotal role in regulating HA-mediated functions as well as Src kinase activity and prostate tumor cell transformation.","PeriodicalId":9675,"journal":{"name":"Cell motility and the cytoskeleton","volume":"22 12","pages":"209-22"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50667416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Actin-based vesicle dynamics and exocytosis during wound wall formation. Video supplement.","authors":"I Foissner,&nbsp;I K Lichtscheidl,&nbsp;G O Wasteneys","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":9675,"journal":{"name":"Cell motility and the cytoskeleton","volume":"39 4","pages":"346-7"},"PeriodicalIF":0.0,"publicationDate":"1998-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20478891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}