Werner Franke - Academia.edu (original) (raw)

Papers by Werner Franke

Research paper thumbnail of A novel kind of tumor type-characteristic junction: plakophilin-2 as a major protein of adherens junctions in cardiac myxomata

Modern Pathology, 2010

Using novel antibodies of high avidity to-and specificity for-the constitutive desmosomal plaque ... more Using novel antibodies of high avidity to-and specificity for-the constitutive desmosomal plaque protein, plakophilin-2 (Pkp2), in a systematic study of the molecular composition of junctions connecting the cells of soft tissue tumors, we have discovered with immunocytochemical, biochemical and electron microscopical methods, a novel type of adherens junctions in all 32 cardiac myxomata examined. These junctions contain cadherin-11 as their major transmembrane glycoprotein, which we could repeatedly show in colocalization with N-cadherin, anchored in a cytoplasmic plaque formed by a-and b-catenin, together with the further armadillo-type proteins plakoglobin, p120, p0071 and ARVCF. Surprisingly, all adherens junctions of these tumors contained, in addition, another major armadillo protein Pkp2, hitherto known as an obligatory and characteristic constituent of desmosomes in epithelium-derived tumors. We have not detected Pkp2 in a series of noncardiac myxomata studied in parallel. Therefore, we conclude that this acquisition of Pkp2, which we have recently also observed in some mesenchymally derived cells growing in culture, can also occur in tumorigenic transformations in situ. We propose to examine the marker value of Pkp2 in clinical diagnoses of cardiac myxomata and to develop Pkp2-targeted therapeutic reagents.

Research paper thumbnail of The nuclear envelope and the architecture of the nuclear periphery

The Journal of Cell Biology, 1981

... in both membranes, the nuclear envelope and AL, and have identical ultrastructure: annular gr... more ... in both membranes, the nuclear envelope and AL, and have identical ultrastructure: annular granules lie on either pore margin and cones of dense material protrude from the membranous walls of the pore into the pore lumen; often a centrally located granule or rod-like element ...

Research paper thumbnail of Actinomycin D and the central granules in the nuclear pore complex: Thin sectioning versus negative staining

Zeitschrift f�r Zellforschung und Mikroskopische Anatomie, 1972

... Z. Zellforsch. 119, 577-604 (1971). Franke, WW, :Falk, H. : Appearance of nuclear pore comple... more ... Z. Zellforsch. 119, 577-604 (1971). Franke, WW, :Falk, H. : Appearance of nuclear pore complexes after Bernhard's staining procedure. ... Biol., in press (1972). Schecr, U., Franke, WW: ]Negative staining and adenosine triphosphatase activity of annulate lamellae of newt oocytes. ...

Research paper thumbnail of Identification and localization of a novel nucleolar protein of high molecular weight by a monoclonal antibody

Experimental Cell Research, 1984

... Identification and localization of a novel nucleolar protein of high molecular weight by a mo... more ... Identification and localization of a novel nucleolar protein of high molecular weight by a monoclonal antibody *1. Marion S. Schmidt-Zachmann , Barbara Hügle , Ulrich Scheer and Werner W. Franke. Division of Membrane Biology ...

Research paper thumbnail of Morphology of Transcriptional Units at Different States of Activity

Philosophical Transactions of the Royal Society B: Biological Sciences, 1978

The morphology of two forms of transcriptionally active chromatin, the nucleoli and the loops of ... more The morphology of two forms of transcriptionally active chromatin, the nucleoli and the loops of lampbrush chromosomes, has been examined after fixation in situ or after isolation and dispersion of the material in media of low ionic strengths, using a variety of electron microscopic preparation techniques (e.g. spread preparations with positive or negative staining or without any staining at all,

Research paper thumbnail of Ribocharin: a nuclear Mr 40,000 protein specific to precursor particles of the large ribosomal subunit

Research paper thumbnail of Natural segregation of nucleolar components in the course of a plant cell differentiation

Planta, 1973

Segregation of the nucleolar components is described in the differentiated nucleus of the generat... more Segregation of the nucleolar components is described in the differentiated nucleus of the generative cell in the growing Clivia and Lilium pollen tubes. This finding of a natural nucleolar segregation is discussed against the background of current views of the correlations of nucleolar morphology and transcriptional activity.

Research paper thumbnail of Frequencies of Circular Units of Nucleolar DNA in Oocytes of Two Insects, Acheta domesticus and Dytiscus marginalis, and Changes of Nucleolar Morphology during Oogenesis

Differentiation, 1977

The organization of the extrachromosomal nucleolar material in oocytes of two insect species with... more The organization of the extrachromosomal nucleolar material in oocytes of two insect species with different ovary types, the house cricket Acheta domesticus (panoistic ovary) and the water beetle Dytiscus marginalis (meroistic ovary), was studied with light and electron microscopic techniques. Stages early in oogenesis were compared with fully vitellogenic stages (mid-to-late diplotene). The arrangement of the nucleolar material undergoes a marked change from a densely aggregated to a dispersed state. The latter was characterized by high transcriptional activity. In spread and positively stained preparations of isolated nucleolar material, a high frequency of small circular units of transcribed rDNA was observed and rings with small numbers (1-5) of pre-rRNA genes were predominant. The observations suggest that the "extra DNA body" observed in early oogenic stages of both species represents a dense aggregate of numerous short circular units of nucleolar chromatin, with morphological subcomponents identifiable in ultrathin sections. These apparently remain in close association with the chromosomal nucleolar organizer@). The observations further indicate that the individual small nucleolar subunit circles dissociate and are dispersed as actively transcribed rDNA units later in diplotene. The results are discussed in relation to principles of the ultrastructural organization of nucleoli in other cell types as well as in relation to possible mechanisms of gene amplification.

Research paper thumbnail of The ultrastructure of the nuclear envelope of amphibian oocytes: a reinvestigation I. The mature oocyte

Journal of Ultrastructure Research, 1970

Research paper thumbnail of Transcription of ribosomal RNA cistrons

Experimental Cell Research, 1973

Electron microscopic spread preparations of oocyte nucleoli (lampbrush stage) of various amphibia... more Electron microscopic spread preparations of oocyte nucleoli (lampbrush stage) of various amphibians are quantitatively evaluated and the length distributions of repeat-, matrix-, and spacer-units along the rRNA cistron containing axes are given. The correlation of the matrix unit data with the gel electrophoretic pattern of labelled nuclear RNA from the same oocytes is examined. The mean value of the matrix unit corresponds fairly well to a 2.6 million D peak of pre-rRNA but the distribution of both matrix units and labelled pre-rRNAs shows an asymmetrical heterogeneity indicating the existence of some larger primary transcription products of rDNA. Novel structural aspects are described in the spacer regions which suggest that transcription does also take place in DNP regions between the matrix units. A special 'prelude piece' coding for approx. 0.5 million D of RNA is frequently visualized in the spacer segments at the beginning of a matrix unit. Possible artifacts resulting from the preparation, the relative congruence between the data obtained using both methods, and the functional meaning of the findings are discussed against the background of current concepts of structural organization and transcription products of nucleolar DNA.

Research paper thumbnail of Cessation of cytokeratin expression in a rat hepatoma cell line lacking differentiated functions

Nature

Intermediate-sized filaments (IF) of diameter 7-11 nm occur in the cytoplasm of most cells of ver... more Intermediate-sized filaments (IF) of diameter 7-11 nm occur in the cytoplasm of most cells of vertebrates and their constituent proteins are abundant in most cell types. Expression of IF proteins depends on the route of cell differentiation and five major subclasses of IF proteins have been distinguished: of these, cytokeratins are typical of epithelial cells whereas vimentin occurs in mesenchymally derived cells and some other non-epithelial cells. When epithelial cells are grown in culture this restriction of IF expression is often lost and they begin to synthesize vimentin in addition to cytokeratin, although examples of maintenance of the cell-type-specific expression of only cytokeratin have also been reported. No IFs have been detected in mammalian germ cells or in pre-morula stages of mouse embryogenesis, and the first IF proteins identified in murine blastocysts are cytokeratins of trophectodermal cells. We report here that a dedifferentiated rat hepatoma cell clone, which h...

Research paper thumbnail of Cytokeratin 8 Protects from Hepatotoxicity, and Its Ratio to Cytokeratin 18 Determines the Ability of Hepatocytes to Form Mallory Bodies

The American Journal of Pathology, 2000

In alcoholic hepatitis, a severe form of alcohol-induced toxic liver injury, as well as in experi... more In alcoholic hepatitis, a severe form of alcohol-induced toxic liver injury, as well as in experimental intoxication of mice with the porphyrinogenic drugs griseofulvin and 3,5-diethoxycarbonyl-1,4-dihydrocollidine, hepatocytes form cytoplasmic protein aggregates (Mallory bodies; MBs) containing cytokeratins (CKs) and non-CK components. Here we report that mice lacking the CK8 gene and hence CK intermediate filaments in hepatocytes, but still expressing the type I partner, ie, the CK18 gene, do not form MBs but suffer from extensive porphyria and progressive toxic liver damage, leading to the death of a considerable number of animals (7 of 12 during 12 weeks of intoxication). Our observations show that 1) in the absence of CK8 as well as in the situation of a relative excess of CK18 over CK8 no MBs are formed; 2) the loss of CK8 is not compensated by other type II CKs; and 3) porphyria and toxic liver damage are drastically enhanced in the absence of CK8. Our results point to a protective role of CKs in certain types of toxic liver injury and suggest that MBs by themselves are not harmful to hepatocytes but may be considered as a product of a novel defense mechanism in hepa-

Research paper thumbnail of A novel kind of tumor type-characteristic junction: plakophilin-2 as a major protein of adherens junctions in cardiac myxomata

Modern Pathology, 2010

Using novel antibodies of high avidity to-and specificity for-the constitutive desmosomal plaque ... more Using novel antibodies of high avidity to-and specificity for-the constitutive desmosomal plaque protein, plakophilin-2 (Pkp2), in a systematic study of the molecular composition of junctions connecting the cells of soft tissue tumors, we have discovered with immunocytochemical, biochemical and electron microscopical methods, a novel type of adherens junctions in all 32 cardiac myxomata examined. These junctions contain cadherin-11 as their major transmembrane glycoprotein, which we could repeatedly show in colocalization with N-cadherin, anchored in a cytoplasmic plaque formed by a-and b-catenin, together with the further armadillo-type proteins plakoglobin, p120, p0071 and ARVCF. Surprisingly, all adherens junctions of these tumors contained, in addition, another major armadillo protein Pkp2, hitherto known as an obligatory and characteristic constituent of desmosomes in epithelium-derived tumors. We have not detected Pkp2 in a series of noncardiac myxomata studied in parallel. Therefore, we conclude that this acquisition of Pkp2, which we have recently also observed in some mesenchymally derived cells growing in culture, can also occur in tumorigenic transformations in situ. We propose to examine the marker value of Pkp2 in clinical diagnoses of cardiac myxomata and to develop Pkp2-targeted therapeutic reagents.

Research paper thumbnail of The nuclear envelope and the architecture of the nuclear periphery

The Journal of Cell Biology, 1981

... in both membranes, the nuclear envelope and AL, and have identical ultrastructure: annular gr... more ... in both membranes, the nuclear envelope and AL, and have identical ultrastructure: annular granules lie on either pore margin and cones of dense material protrude from the membranous walls of the pore into the pore lumen; often a centrally located granule or rod-like element ...

Research paper thumbnail of Actinomycin D and the central granules in the nuclear pore complex: Thin sectioning versus negative staining

Zeitschrift f�r Zellforschung und Mikroskopische Anatomie, 1972

... Z. Zellforsch. 119, 577-604 (1971). Franke, WW, :Falk, H. : Appearance of nuclear pore comple... more ... Z. Zellforsch. 119, 577-604 (1971). Franke, WW, :Falk, H. : Appearance of nuclear pore complexes after Bernhard's staining procedure. ... Biol., in press (1972). Schecr, U., Franke, WW: ]Negative staining and adenosine triphosphatase activity of annulate lamellae of newt oocytes. ...

Research paper thumbnail of Identification and localization of a novel nucleolar protein of high molecular weight by a monoclonal antibody

Experimental Cell Research, 1984

... Identification and localization of a novel nucleolar protein of high molecular weight by a mo... more ... Identification and localization of a novel nucleolar protein of high molecular weight by a monoclonal antibody *1. Marion S. Schmidt-Zachmann , Barbara Hügle , Ulrich Scheer and Werner W. Franke. Division of Membrane Biology ...

Research paper thumbnail of Morphology of Transcriptional Units at Different States of Activity

Philosophical Transactions of the Royal Society B: Biological Sciences, 1978

The morphology of two forms of transcriptionally active chromatin, the nucleoli and the loops of ... more The morphology of two forms of transcriptionally active chromatin, the nucleoli and the loops of lampbrush chromosomes, has been examined after fixation in situ or after isolation and dispersion of the material in media of low ionic strengths, using a variety of electron microscopic preparation techniques (e.g. spread preparations with positive or negative staining or without any staining at all,

Research paper thumbnail of Ribocharin: a nuclear Mr 40,000 protein specific to precursor particles of the large ribosomal subunit

Research paper thumbnail of Natural segregation of nucleolar components in the course of a plant cell differentiation

Planta, 1973

Segregation of the nucleolar components is described in the differentiated nucleus of the generat... more Segregation of the nucleolar components is described in the differentiated nucleus of the generative cell in the growing Clivia and Lilium pollen tubes. This finding of a natural nucleolar segregation is discussed against the background of current views of the correlations of nucleolar morphology and transcriptional activity.

Research paper thumbnail of Frequencies of Circular Units of Nucleolar DNA in Oocytes of Two Insects, Acheta domesticus and Dytiscus marginalis, and Changes of Nucleolar Morphology during Oogenesis

Differentiation, 1977

The organization of the extrachromosomal nucleolar material in oocytes of two insect species with... more The organization of the extrachromosomal nucleolar material in oocytes of two insect species with different ovary types, the house cricket Acheta domesticus (panoistic ovary) and the water beetle Dytiscus marginalis (meroistic ovary), was studied with light and electron microscopic techniques. Stages early in oogenesis were compared with fully vitellogenic stages (mid-to-late diplotene). The arrangement of the nucleolar material undergoes a marked change from a densely aggregated to a dispersed state. The latter was characterized by high transcriptional activity. In spread and positively stained preparations of isolated nucleolar material, a high frequency of small circular units of transcribed rDNA was observed and rings with small numbers (1-5) of pre-rRNA genes were predominant. The observations suggest that the "extra DNA body" observed in early oogenic stages of both species represents a dense aggregate of numerous short circular units of nucleolar chromatin, with morphological subcomponents identifiable in ultrathin sections. These apparently remain in close association with the chromosomal nucleolar organizer@). The observations further indicate that the individual small nucleolar subunit circles dissociate and are dispersed as actively transcribed rDNA units later in diplotene. The results are discussed in relation to principles of the ultrastructural organization of nucleoli in other cell types as well as in relation to possible mechanisms of gene amplification.

Research paper thumbnail of The ultrastructure of the nuclear envelope of amphibian oocytes: a reinvestigation I. The mature oocyte

Journal of Ultrastructure Research, 1970

Research paper thumbnail of Transcription of ribosomal RNA cistrons

Experimental Cell Research, 1973

Electron microscopic spread preparations of oocyte nucleoli (lampbrush stage) of various amphibia... more Electron microscopic spread preparations of oocyte nucleoli (lampbrush stage) of various amphibians are quantitatively evaluated and the length distributions of repeat-, matrix-, and spacer-units along the rRNA cistron containing axes are given. The correlation of the matrix unit data with the gel electrophoretic pattern of labelled nuclear RNA from the same oocytes is examined. The mean value of the matrix unit corresponds fairly well to a 2.6 million D peak of pre-rRNA but the distribution of both matrix units and labelled pre-rRNAs shows an asymmetrical heterogeneity indicating the existence of some larger primary transcription products of rDNA. Novel structural aspects are described in the spacer regions which suggest that transcription does also take place in DNP regions between the matrix units. A special 'prelude piece' coding for approx. 0.5 million D of RNA is frequently visualized in the spacer segments at the beginning of a matrix unit. Possible artifacts resulting from the preparation, the relative congruence between the data obtained using both methods, and the functional meaning of the findings are discussed against the background of current concepts of structural organization and transcription products of nucleolar DNA.

Research paper thumbnail of Cessation of cytokeratin expression in a rat hepatoma cell line lacking differentiated functions

Nature

Intermediate-sized filaments (IF) of diameter 7-11 nm occur in the cytoplasm of most cells of ver... more Intermediate-sized filaments (IF) of diameter 7-11 nm occur in the cytoplasm of most cells of vertebrates and their constituent proteins are abundant in most cell types. Expression of IF proteins depends on the route of cell differentiation and five major subclasses of IF proteins have been distinguished: of these, cytokeratins are typical of epithelial cells whereas vimentin occurs in mesenchymally derived cells and some other non-epithelial cells. When epithelial cells are grown in culture this restriction of IF expression is often lost and they begin to synthesize vimentin in addition to cytokeratin, although examples of maintenance of the cell-type-specific expression of only cytokeratin have also been reported. No IFs have been detected in mammalian germ cells or in pre-morula stages of mouse embryogenesis, and the first IF proteins identified in murine blastocysts are cytokeratins of trophectodermal cells. We report here that a dedifferentiated rat hepatoma cell clone, which h...

Research paper thumbnail of Cytokeratin 8 Protects from Hepatotoxicity, and Its Ratio to Cytokeratin 18 Determines the Ability of Hepatocytes to Form Mallory Bodies

The American Journal of Pathology, 2000

In alcoholic hepatitis, a severe form of alcohol-induced toxic liver injury, as well as in experi... more In alcoholic hepatitis, a severe form of alcohol-induced toxic liver injury, as well as in experimental intoxication of mice with the porphyrinogenic drugs griseofulvin and 3,5-diethoxycarbonyl-1,4-dihydrocollidine, hepatocytes form cytoplasmic protein aggregates (Mallory bodies; MBs) containing cytokeratins (CKs) and non-CK components. Here we report that mice lacking the CK8 gene and hence CK intermediate filaments in hepatocytes, but still expressing the type I partner, ie, the CK18 gene, do not form MBs but suffer from extensive porphyria and progressive toxic liver damage, leading to the death of a considerable number of animals (7 of 12 during 12 weeks of intoxication). Our observations show that 1) in the absence of CK8 as well as in the situation of a relative excess of CK18 over CK8 no MBs are formed; 2) the loss of CK8 is not compensated by other type II CKs; and 3) porphyria and toxic liver damage are drastically enhanced in the absence of CK8. Our results point to a protective role of CKs in certain types of toxic liver injury and suggest that MBs by themselves are not harmful to hepatocytes but may be considered as a product of a novel defense mechanism in hepa-