The Drosophila lethal(2)giant larvae tumor suppressor protein is a component of the cytoskeleton
Tumor suppressor genes act as recessive determinants of cancer. In Drosophila these genes play a role in normal development and are essential for regulating cell growth and differentiation. Mutations in the gene, lethal(2)giant larvae, l(2)gl, besides causing malignant tumors in the brain and imagin...
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| Veröffentlicht in: | The Journal of cell biology 1994-12, Vol.127 (5), p.1345-1360 |
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| container_title | The Journal of cell biology |
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| creator | Strand, Dennis Raska, Ivan Mechler, Bernard M. |
| description | Tumor suppressor genes act as recessive determinants of cancer. In Drosophila these genes play a role in normal development and are essential for regulating cell growth and differentiation. Mutations in the gene, lethal(2)giant larvae, l(2)gl, besides causing malignant tumors in the brain and imaginal discs, generate developmental defects in a number of other tissues. Much of the uncertainty regarding the function of the l(2)gl gene product, p127, results from a lack of knowledge as to the precise location of this protein in the cell. We have investigated the cellular and subcellular localization of p127, using confocal and electron microscopy as well as biochemical and cell fractionation procedures. Our analyses indicate that p127 is located entirely within the cell in both the cytoplasm and bound to the inner face of lateral cell membranes in regions of cell junctions. On the membrane, p127 can form large aggregates which are resistant to solubilization by nonionic detergents, indicating that p127 is participating in a cytoskeletal matrix. These findings suggest that the changes in cell shape and the loss of apical-basal polarity observed in tumorous tissues are a direct result of alterations in the cytoskeleton organization caused by 1(2)gl inactivation and also suggest that p127 is involved in a cytoskeletal-based intercellular communication system directing cell differentiation. |
| doi_str_mv | 10.1083/jcb.127.5.1345 |
| format | Article |
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In Drosophila these genes play a role in normal development and are essential for regulating cell growth and differentiation. Mutations in the gene, lethal(2)giant larvae, l(2)gl, besides causing malignant tumors in the brain and imaginal discs, generate developmental defects in a number of other tissues. Much of the uncertainty regarding the function of the l(2)gl gene product, p127, results from a lack of knowledge as to the precise location of this protein in the cell. We have investigated the cellular and subcellular localization of p127, using confocal and electron microscopy as well as biochemical and cell fractionation procedures. Our analyses indicate that p127 is located entirely within the cell in both the cytoplasm and bound to the inner face of lateral cell membranes in regions of cell junctions. On the membrane, p127 can form large aggregates which are resistant to solubilization by nonionic detergents, indicating that p127 is participating in a cytoskeletal matrix. These findings suggest that the changes in cell shape and the loss of apical-basal polarity observed in tumorous tissues are a direct result of alterations in the cytoskeleton organization caused by 1(2)gl inactivation and also suggest that p127 is involved in a cytoskeletal-based intercellular communication system directing cell differentiation.</description><identifier>ISSN: 0021-9525</identifier><identifier>EISSN: 1540-8140</identifier><identifier>DOI: 10.1083/jcb.127.5.1345</identifier><identifier>PMID: 7962094</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Amino Acid Sequence ; Animals ; Antibodies ; Cell Line ; Cell Membrane - chemistry ; Cell membranes ; cell structure ; Cells ; citoplasma ; cytoplasm ; Cytoplasm - chemistry ; cytoplasme ; Cytoskeleton - chemistry ; Drosophila ; drosophila melanogaster ; Drosophila melanogaster - chemistry ; Drosophila melanogaster - embryology ; Drosophila melanogaster - genetics ; Drosophila melanogaster - growth & development ; Drosophila Proteins ; Embryo, Nonmammalian - chemistry ; Embryonic cells ; Embryos ; estructura celular ; Female ; Genes, Insect ; Germ cells ; Imaginal discs ; immunologie ; immunology ; inmunologia ; Insect Hormones - analysis ; Insect Hormones - genetics ; Insect Hormones - metabolism ; Larva - chemistry ; Larvae ; Larval development ; Male ; Microscopy, Immunoelectron ; Molecular Sequence Data ; proteinas ; proteine ; proteins ; structure cellulaire ; Subcellular Fractions ; Tumor Suppressor Proteins ; ultraestructura ; ultrastructure</subject><ispartof>The Journal of cell biology, 1994-12, Vol.127 (5), p.1345-1360</ispartof><rights>Copyright 1994 The Rockefeller University Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-cce2a04cdf77462ecccd26cad92c7fc9358f52c10513d4087b6863daedd0177a3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7962094$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Strand, Dennis</creatorcontrib><creatorcontrib>Raska, Ivan</creatorcontrib><creatorcontrib>Mechler, Bernard M.</creatorcontrib><creatorcontrib>Deutsches Krebsforschungszentrum, Heidelberg, Germany</creatorcontrib><title>The Drosophila lethal(2)giant larvae tumor suppressor protein is a component of the cytoskeleton</title><title>The Journal of cell biology</title><addtitle>J Cell Biol</addtitle><description>Tumor suppressor genes act as recessive determinants of cancer. In Drosophila these genes play a role in normal development and are essential for regulating cell growth and differentiation. Mutations in the gene, lethal(2)giant larvae, l(2)gl, besides causing malignant tumors in the brain and imaginal discs, generate developmental defects in a number of other tissues. Much of the uncertainty regarding the function of the l(2)gl gene product, p127, results from a lack of knowledge as to the precise location of this protein in the cell. We have investigated the cellular and subcellular localization of p127, using confocal and electron microscopy as well as biochemical and cell fractionation procedures. Our analyses indicate that p127 is located entirely within the cell in both the cytoplasm and bound to the inner face of lateral cell membranes in regions of cell junctions. On the membrane, p127 can form large aggregates which are resistant to solubilization by nonionic detergents, indicating that p127 is participating in a cytoskeletal matrix. These findings suggest that the changes in cell shape and the loss of apical-basal polarity observed in tumorous tissues are a direct result of alterations in the cytoskeleton organization caused by 1(2)gl inactivation and also suggest that p127 is involved in a cytoskeletal-based intercellular communication system directing cell differentiation.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Cell Line</subject><subject>Cell Membrane - chemistry</subject><subject>Cell membranes</subject><subject>cell structure</subject><subject>Cells</subject><subject>citoplasma</subject><subject>cytoplasm</subject><subject>Cytoplasm - chemistry</subject><subject>cytoplasme</subject><subject>Cytoskeleton - chemistry</subject><subject>Drosophila</subject><subject>drosophila melanogaster</subject><subject>Drosophila melanogaster - chemistry</subject><subject>Drosophila melanogaster - embryology</subject><subject>Drosophila melanogaster - genetics</subject><subject>Drosophila melanogaster - growth & development</subject><subject>Drosophila Proteins</subject><subject>Embryo, Nonmammalian - chemistry</subject><subject>Embryonic cells</subject><subject>Embryos</subject><subject>estructura celular</subject><subject>Female</subject><subject>Genes, Insect</subject><subject>Germ cells</subject><subject>Imaginal discs</subject><subject>immunologie</subject><subject>immunology</subject><subject>inmunologia</subject><subject>Insect Hormones - analysis</subject><subject>Insect Hormones - genetics</subject><subject>Insect Hormones - metabolism</subject><subject>Larva - chemistry</subject><subject>Larvae</subject><subject>Larval development</subject><subject>Male</subject><subject>Microscopy, Immunoelectron</subject><subject>Molecular Sequence Data</subject><subject>proteinas</subject><subject>proteine</subject><subject>proteins</subject><subject>structure cellulaire</subject><subject>Subcellular Fractions</subject><subject>Tumor Suppressor Proteins</subject><subject>ultraestructura</subject><subject>ultrastructure</subject><issn>0021-9525</issn><issn>1540-8140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtv1DAURi1EVYaBLStAXiG6SLh-JxskVB5FqsSCdm08jjPjIYlT26nUf19XMyqwYmVL3_HR9f0QekWgJtCwD3u7qQlVtagJ4-IJWhHBoWoIh6doBUBJ1QoqnqHnKe0BgCvOTtGpaiWFlq_Qr6udw59jSGHe-cHgweWdGd7Ts603U8aDibfG4byMIeK0zHN0KZXrHEN2fsI-YYNtGOcwuYKHHufis3c5pN-uuML0Ap30Zkju5fFco-uvX67OL6rLH9--n3-6rKygMlfWOmqA265XikvqrLUdldZ0LbWqty0TTS-oJSAI6zg0aiMbyTrjug6IUoat0ceDd142o-tsGSeaQc_Rjybe6WC8_jeZ_E5vw62mhAKVrAjeHQUx3CwuZT36ZN0wmMmFJWklG0pE-3-QSNUoxmUB6wNoy35TdP3jNAT0Q3m6lKdLeVroh_LKgzd__-ERP7ZV8teHfJ9yiH9skkhR9rJGbw9xb4I22-iTvv5J2lYAEY0SwO4B7DWqqA</recordid><startdate>19941201</startdate><enddate>19941201</enddate><creator>Strand, Dennis</creator><creator>Raska, Ivan</creator><creator>Mechler, Bernard M.</creator><general>Rockefeller University Press</general><general>The Rockefeller University Press</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SS</scope><scope>7TK</scope><scope>7TO</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>19941201</creationdate><title>The Drosophila lethal(2)giant larvae tumor suppressor protein is a component of the cytoskeleton</title><author>Strand, Dennis ; Raska, Ivan ; Mechler, Bernard M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-cce2a04cdf77462ecccd26cad92c7fc9358f52c10513d4087b6863daedd0177a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Cell Line</topic><topic>Cell Membrane - chemistry</topic><topic>Cell membranes</topic><topic>cell structure</topic><topic>Cells</topic><topic>citoplasma</topic><topic>cytoplasm</topic><topic>Cytoplasm - chemistry</topic><topic>cytoplasme</topic><topic>Cytoskeleton - chemistry</topic><topic>Drosophila</topic><topic>drosophila melanogaster</topic><topic>Drosophila melanogaster - chemistry</topic><topic>Drosophila melanogaster - embryology</topic><topic>Drosophila melanogaster - genetics</topic><topic>Drosophila melanogaster - growth & development</topic><topic>Drosophila Proteins</topic><topic>Embryo, Nonmammalian - chemistry</topic><topic>Embryonic cells</topic><topic>Embryos</topic><topic>estructura celular</topic><topic>Female</topic><topic>Genes, Insect</topic><topic>Germ cells</topic><topic>Imaginal discs</topic><topic>immunologie</topic><topic>immunology</topic><topic>inmunologia</topic><topic>Insect Hormones - analysis</topic><topic>Insect Hormones - genetics</topic><topic>Insect Hormones - metabolism</topic><topic>Larva - chemistry</topic><topic>Larvae</topic><topic>Larval development</topic><topic>Male</topic><topic>Microscopy, Immunoelectron</topic><topic>Molecular Sequence Data</topic><topic>proteinas</topic><topic>proteine</topic><topic>proteins</topic><topic>structure cellulaire</topic><topic>Subcellular Fractions</topic><topic>Tumor Suppressor Proteins</topic><topic>ultraestructura</topic><topic>ultrastructure</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Strand, Dennis</creatorcontrib><creatorcontrib>Raska, Ivan</creatorcontrib><creatorcontrib>Mechler, Bernard M.</creatorcontrib><creatorcontrib>Deutsches Krebsforschungszentrum, Heidelberg, Germany</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of cell biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Strand, Dennis</au><au>Raska, Ivan</au><au>Mechler, Bernard M.</au><aucorp>Deutsches Krebsforschungszentrum, Heidelberg, Germany</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Drosophila lethal(2)giant larvae tumor suppressor protein is a component of the cytoskeleton</atitle><jtitle>The Journal of cell biology</jtitle><addtitle>J Cell Biol</addtitle><date>1994-12-01</date><risdate>1994</risdate><volume>127</volume><issue>5</issue><spage>1345</spage><epage>1360</epage><pages>1345-1360</pages><issn>0021-9525</issn><eissn>1540-8140</eissn><abstract>Tumor suppressor genes act as recessive determinants of cancer. In Drosophila these genes play a role in normal development and are essential for regulating cell growth and differentiation. Mutations in the gene, lethal(2)giant larvae, l(2)gl, besides causing malignant tumors in the brain and imaginal discs, generate developmental defects in a number of other tissues. Much of the uncertainty regarding the function of the l(2)gl gene product, p127, results from a lack of knowledge as to the precise location of this protein in the cell. We have investigated the cellular and subcellular localization of p127, using confocal and electron microscopy as well as biochemical and cell fractionation procedures. Our analyses indicate that p127 is located entirely within the cell in both the cytoplasm and bound to the inner face of lateral cell membranes in regions of cell junctions. On the membrane, p127 can form large aggregates which are resistant to solubilization by nonionic detergents, indicating that p127 is participating in a cytoskeletal matrix. These findings suggest that the changes in cell shape and the loss of apical-basal polarity observed in tumorous tissues are a direct result of alterations in the cytoskeleton organization caused by 1(2)gl inactivation and also suggest that p127 is involved in a cytoskeletal-based intercellular communication system directing cell differentiation.</abstract><cop>United States</cop><pub>Rockefeller University Press</pub><pmid>7962094</pmid><doi>10.1083/jcb.127.5.1345</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amino Acid Sequence Animals Antibodies Cell Line Cell Membrane - chemistry Cell membranes cell structure Cells citoplasma cytoplasm Cytoplasm - chemistry cytoplasme Cytoskeleton - chemistry Drosophila drosophila melanogaster Drosophila melanogaster - chemistry Drosophila melanogaster - embryology Drosophila melanogaster - genetics Drosophila melanogaster - growth & development Drosophila Proteins Embryo, Nonmammalian - chemistry Embryonic cells Embryos estructura celular Female Genes, Insect Germ cells Imaginal discs immunologie immunology inmunologia Insect Hormones - analysis Insect Hormones - genetics Insect Hormones - metabolism Larva - chemistry Larvae Larval development Male Microscopy, Immunoelectron Molecular Sequence Data proteinas proteine proteins structure cellulaire Subcellular Fractions Tumor Suppressor Proteins ultraestructura ultrastructure |
| title | The Drosophila lethal(2)giant larvae tumor suppressor protein is a component of the cytoskeleton |
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