Controlled Elimination of Clathrin Heavy-Chain Expression in DT40 Lymphocytes
We exploited the high rate of homologous recombination shown by the chicken B cell line DT40 to inactivate the endogenous alleles for clathrin heavy chain and replace them with human clathrin complementary DNA under the control of a tetracycline-regulatable promoter. Clathrin repression perturbed th...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2002-08, Vol.297 (5586), p.1521-1525 |
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| creator | Wettey, Frank R. Steve F. C. Hawkins Stewart, Abigail Luzio, J. Paul Howard, Jonathan C. Jackson, Antony P. |
| description | We exploited the high rate of homologous recombination shown by the chicken B cell line DT40 to inactivate the endogenous alleles for clathrin heavy chain and replace them with human clathrin complementary DNA under the control of a tetracycline-regulatable promoter. Clathrin repression perturbed the activities of Akt-mediated and mitogen-activated protein kinase-mediated signaling pathways and induced apoptosis; this finding suggests that in DT40 cells clathrin helps to maintain the integrity of antiapoptotic survival pathways. We also describe a variant cell line in which these signaling pathways were unaffected by clathrin down-regulation. This variant cell line did not undergo apoptosis in the absence of clathrin and was used to examine the effects of clathrin depletion on membrane-trafficking pathways. Receptor-mediated and fluid-phase endocytosis were both substantially inhibited, and transferrin-receptor recycling was modestly inhibited. Surprisingly, clathrin removal did not affect the morphology or biochemical composition of lysosomes. |
| doi_str_mv | 10.1126/science.1074222 |
| format | Article |
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This variant cell line did not undergo apoptosis in the absence of clathrin and was used to examine the effects of clathrin depletion on membrane-trafficking pathways. Receptor-mediated and fluid-phase endocytosis were both substantially inhibited, and transferrin-receptor recycling was modestly inhibited. 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Psychology ; Gene Expression Regulation - drug effects ; Genetics ; Lysosomes ; Lysosomes - physiology ; Membrane Proteins - physiology ; Molecular and cellular biology ; Molecular Sequence Data ; Recycling ; Signal Transduction</subject><ispartof>Science (American Association for the Advancement of Science), 2002-08, Vol.297 (5586), p.1521-1525</ispartof><rights>Copyright 2002 American Association for the Advancement of Science</rights><rights>2002 INIST-CNRS</rights><rights>COPYRIGHT 2002 American Association for the Advancement of Science</rights><rights>COPYRIGHT 2002 American Association for the Advancement of Science</rights><rights>Copyright American Association for the Advancement of Science Aug 30, 2002</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c775t-be0019cf8e086b45c00af93af53ca47c2fbbd7a6892f90c5586b5ef2c3ee73873</citedby><cites>FETCH-LOGICAL-c775t-be0019cf8e086b45c00af93af53ca47c2fbbd7a6892f90c5586b5ef2c3ee73873</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3832488$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3832488$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>314,778,782,801,2873,2874,27907,27908,58000,58233</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13893971$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12202821$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wettey, Frank R.</creatorcontrib><creatorcontrib>Steve F. 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We also describe a variant cell line in which these signaling pathways were unaffected by clathrin down-regulation. This variant cell line did not undergo apoptosis in the absence of clathrin and was used to examine the effects of clathrin depletion on membrane-trafficking pathways. Receptor-mediated and fluid-phase endocytosis were both substantially inhibited, and transferrin-receptor recycling was modestly inhibited. Surprisingly, clathrin removal did not affect the morphology or biochemical composition of lysosomes.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>B lymphocytes</subject><subject>B-Lymphocytes - metabolism</subject><subject>B-Lymphocytes - ultrastructure</subject><subject>Biological and medical sciences</subject><subject>Cell growth</subject><subject>Cell Line</subject><subject>Cell lines</subject><subject>Cell membranes</subject><subject>Cell physiology</subject><subject>Cells</subject><subject>Cells (Biology)</subject><subject>Cellular biology</subject><subject>Cerebrospinal fluid proteins</subject><subject>Chickens</subject><subject>Clathrin</subject><subject>Clathrin - biosynthesis</subject><subject>Clathrin - genetics</subject><subject>Clathrin - physiology</subject><subject>Clathrin Heavy Chains</subject><subject>Down-Regulation</subject><subject>Doxycycline - pharmacology</subject><subject>Endocytosis</subject><subject>Endocytosis - physiology</subject><subject>Eukaryotes</subject><subject>Eukaryotic cells</subject><subject>Fundamental and applied biological sciences. 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Paul ; Howard, Jonathan C. ; Jackson, Antony P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c775t-be0019cf8e086b45c00af93af53ca47c2fbbd7a6892f90c5586b5ef2c3ee73873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Apoptosis</topic><topic>B lymphocytes</topic><topic>B-Lymphocytes - metabolism</topic><topic>B-Lymphocytes - ultrastructure</topic><topic>Biological and medical sciences</topic><topic>Cell growth</topic><topic>Cell Line</topic><topic>Cell lines</topic><topic>Cell membranes</topic><topic>Cell physiology</topic><topic>Cells</topic><topic>Cells (Biology)</topic><topic>Cellular biology</topic><topic>Cerebrospinal fluid proteins</topic><topic>Chickens</topic><topic>Clathrin</topic><topic>Clathrin - biosynthesis</topic><topic>Clathrin - genetics</topic><topic>Clathrin - physiology</topic><topic>Clathrin Heavy Chains</topic><topic>Down-Regulation</topic><topic>Doxycycline - pharmacology</topic><topic>Endocytosis</topic><topic>Endocytosis - physiology</topic><topic>Eukaryotes</topic><topic>Eukaryotic cells</topic><topic>Fundamental and applied biological sciences. 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Clathrin repression perturbed the activities of Akt-mediated and mitogen-activated protein kinase-mediated signaling pathways and induced apoptosis; this finding suggests that in DT40 cells clathrin helps to maintain the integrity of antiapoptotic survival pathways. We also describe a variant cell line in which these signaling pathways were unaffected by clathrin down-regulation. This variant cell line did not undergo apoptosis in the absence of clathrin and was used to examine the effects of clathrin depletion on membrane-trafficking pathways. Receptor-mediated and fluid-phase endocytosis were both substantially inhibited, and transferrin-receptor recycling was modestly inhibited. Surprisingly, clathrin removal did not affect the morphology or biochemical composition of lysosomes.</abstract><cop>Washington, DC</cop><pub>American Association for the Advancement of Science</pub><pmid>12202821</pmid><doi>10.1126/science.1074222</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2002-08, Vol.297 (5586), p.1521-1525 |
| issn | 0036-8075 1095-9203 |
| language | eng |
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| source | MEDLINE; American Association for the Advancement of Science; Jstor Complete Legacy |
| subjects | Animals Antibodies Apoptosis B lymphocytes B-Lymphocytes - metabolism B-Lymphocytes - ultrastructure Biological and medical sciences Cell growth Cell Line Cell lines Cell membranes Cell physiology Cells Cells (Biology) Cellular biology Cerebrospinal fluid proteins Chickens Clathrin Clathrin - biosynthesis Clathrin - genetics Clathrin - physiology Clathrin Heavy Chains Down-Regulation Doxycycline - pharmacology Endocytosis Endocytosis - physiology Eukaryotes Eukaryotic cells Fundamental and applied biological sciences. Psychology Gene Expression Regulation - drug effects Genetics Lysosomes Lysosomes - physiology Membrane Proteins - physiology Molecular and cellular biology Molecular Sequence Data Recycling Signal Transduction |
| title | Controlled Elimination of Clathrin Heavy-Chain Expression in DT40 Lymphocytes |
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